Effects of growth hormone on insulin sensitivity and forearm metabolism in normal man
Open accessAbstract
To elucidate the short-term actions of growth hormone on insulin sensitivity and forearm metabolism, we have studied six normal male subjects receiving a 6-h hyperinsulinaemic euglycemic clamp with and without a concomitant 4-h growth hormone infusion. When infused, serum growth hormone rose to 25 +/- 4 mU/l and during administration of insulin serum insulin increased by 11 +/- 1 mU/l. During euglycemic clamp, administration of growth hormone decreased forearm glucose uptake after 180 min and onward (240 min 0.216 +/- 0.031 vs 0.530 +/- 0.090 mg/100 ml/min, p less than 0.05). Glucose infusion rate (240 min 2.83 +/- 0.24 vs 4.35 +/- 0.28 mg.kg-1.min-1, p less than 0.05) and glucose disposal rate (240 min 3.57 +/- 0.17 vs 4.00 +/- 0.15 mg.kg-1.min-1, p less than 0.05) also decreased. Growth hormone persistently increased hepatic glucose production after 120 min. After 210 min, all circulating lipid intermediates increased slightly. The decrease in forearm glucose uptake and glucose infusion rate and the increase in hepatic glucose production was observed before there was any detectable increase in circulating levels and forearm uptake of lipid intermediates. These data suggest that growth hormone induces insensitivity to insulin in liver, muscle and fat after 120, 180 and 210 min respectively. The early effects of growth hormone on glucose metabolism seems independent of changes in the rate of lipolysis.
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TL;DR
In six healthy men, a 4-h growth hormone infusion during a 6-h hyperinsulinaemic euglycaemic clamp induced insulin insensitivity in liver, muscle and fat, with hepatic glucose output rising first (120 min), forearm glucose uptake falling at 180 min, and lipid intermediates rising only at 210 min. Because the glucose-handling defects preceded any detectable rise in circulating or forearm-uptake lipid fuels, the authors conclude the early anti-insulin effect of GH on glucose metabolism is independent of lipolysis.
Key findings
- GH reduced forearm glucose uptake by 58% (240 min: 0.216 ± 0.031 vs 0.530 ± 0.090 mg/100 ml/min, p < 0.05), significant from 180 min of GH administration.
- Glucose infusion rate (M-value) fell 36% (240 min: 2.83 ± 0.24 vs 4.35 ± 0.28 mg·kg⁻¹·min⁻¹, p < 0.05) and tracer-determined glucose disposal rate fell 10% (3.57 ± 0.17 vs 4.00 ± 0.15 mg·kg⁻¹·min⁻¹, p < 0.05).
- Hepatic glucose production rose persistently with GH, reaching 0.7 ± 0.2 mg·kg⁻¹·min⁻¹ at 240 min (p < 0.05), significant from 120 min — i.e. before the muscle effect.
- Circulating lipid intermediates rose only late: NEFA to 480 ± 60 µmol/l (p < 0.05, from 210 min), glycerol to 43 ± 6 µmol/l (p < 0.01, from 180 min) and 3-hydroxybutyrate to 30 ± 3 µmol/l (p < 0.05, from 240 min); forearm NEFA uptake was unaffected at all timepoints. Alanine, pyruvate and lactate metabolism were unchanged, and somatomedin-C stayed constant (~27.2 ± 2.2 nmol/l).
Methods
- Design: randomised-order, two-occasion study (≥4 weeks apart) in six healthy normal-weight male volunteers (aged 30 ± 2 years, BMI 21.0 ± 0.7 kg/m²), after a 10-h overnight fast; each subject received a 6-h hyperinsulinaemic euglycaemic clamp alone and the same clamp plus a 4-h GH infusion (4 µg/kg/h for 30 min, then 2.5 µg/kg/h).
- Data: insulin infused at 0.015 U/kg/h to achieve physiological hyperinsulinaemia (serum insulin 4 ± 1 to 15 ± 1 mU/l); [6-³H]glucose infusion with the Steele equation (pool fraction 0.65) for Ra/Rd and hepatic glucose output; deep antecubital venous catheterisation with venous occlusion plethysmography for forearm substrate balance; automated fluorimetric/enzymatic assays and radioimmunoassays.
- Analysis: ANOVA with paired Student's t-tests where appropriate; p < 0.05 (two-tailed) considered significant; results as means ± SEM.
Limitations
- Stated by the authors: the isotope dilution technique may under-estimate hepatic glucose output and fail to detect small changes in glucose turnover (non-steady-state error or isotope discrimination/contamination); tracer equilibration lag may under-estimate the true fall in glucose disposal.
- Evident from the text: the sample is very small (n = 6) and restricted to healthy normal-weight men, so findings may not generalise to women, obesity or pathological GH states; the authors themselves note that the glucose/fatty-acid/ketone cycle may only become important with more sustained GH elevation.
- Evident from the text: the mechanism is inferred rather than measured — the authors propose post-receptor modulation because short-term GH does not interfere with insulin receptor binding, but no receptor or enzyme data are presented here.
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- Findingown data
After insulin administration, plasma NEFA, blood glycerol and 3-hydroxybutyrate fell from basal levels to plateaus.
“After administration of insulin plasma NEFA, blood glycerol and 3-hydroxybutyrate values fell from basal levels of 410+80, 39+6 and 42+9 Ixmol/1 to a plateau of approximately 150+60, 20+5 and 10_+5 ~mol/1 respectively (Table1).”
Quote in the paperNot a substantial claim - Findingown data
At the end of the study, growth hormone had decreased forearm glucose uptake by 58% (with growth hormone 0.22 ± 0.03 vs 0.53 ± 0.09 mg/100 ml/min).
“At the end of the study, GH had decreased forearm glucose uptake by 58% (with GH 0.22 + 0.03 mg/100 ml/min vs 0.53 _+ 0.09 mg/100 ml/min) (Fig. 3).”
Quote in the paperSubstantial claim- The authors state this as an assumption: The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
- The authors state this as an assumption: Red cell intracellular NEFA equilibrate freely with plasma NEFA, and total blood concentration of NEFA can be calculated by multiplying plasma NEFA by (1 - 0.30 × hematocrit).
- The authors state this as an assumption: When catabolised oxidatively, ATP production from one mole of glucose, 3-hydroxybutyrate and NEFA (palmitate) is 38, 30 and 129 moles of ATP respectively.
- Findingown data
The clamped values of arterialised blood glucose did not differ statistically at any time.
“The clamped values of arterialised blood glucose did not differ statistically at any time.”
Quote in the paperNot a substantial claim - Findingown data
During hyperinsulinaemic euglycemia, decreased glucose disposal in the forearm is found before there is any detectable increase in either circulating levels of, or net uptake of alternative fuels.
“The present study, however, shows that during hyperinsulinaemic euglycemia decreased glucose disposal in the forearm is found before there is any detectable increase in either circulating levels of, or net uptake of alternative fuels.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
- The authors state this as an assumption: Red cell intracellular NEFA equilibrate freely with plasma NEFA, and total blood concentration of NEFA can be calculated by multiplying plasma NEFA by (1 - 0.30 × hematocrit).
- The authors state this as an assumption: When catabolised oxidatively, ATP production from one mole of glucose, 3-hydroxybutyrate and NEFA (palmitate) is 38, 30 and 129 moles of ATP respectively.
- Findingown data
Growth hormone infusion increased serum growth hormone from baseline values of 3.2 ± 1.7 mU/l to 31.2 ± 2.8 mU/l after 4 h.
“The GH infusion increased serum GH from baseline values of 3.2 _+ 1.7 mU/1 to a slightly increasing level of 31.2 ___ 2.8 mU/1 after 4 h (Fig. I).”
Quote in the paperSubstantial claim
- Findingown data
The decrease in forearm glucose uptake with growth hormone was statistically significant (p < 0.05) after 180 min of growth hormone administration.
“The decrease was statistically significant (p < 0.05) after 180 min of GH administration.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
- The authors state this as an assumption: Red cell intracellular NEFA equilibrate freely with plasma NEFA, and total blood concentration of NEFA can be calculated by multiplying plasma NEFA by (1 - 0.30 × hematocrit).
- The authors state this as an assumption: When catabolised oxidatively, ATP production from one mole of glucose, 3-hydroxybutyrate and NEFA (palmitate) is 38, 30 and 129 moles of ATP respectively.
- Findingown data
Basal serum somatomedin-C values were not affected by insulin or growth hormone infusions and remained constant around 27.2 ± 2.2 nmol/l.
“Basal serum somatomedin-C values were not affected by insulin or GH infusions and remained constant around a basal level of 27.2 _+ 2.2 nmol/1.”
Quote in the paperNot a substantial claim - Findingown data
Growth hormone administration did not affect any parameters of alanine, pyruvate or lactate metabolism.
“GH administration did not affect any parameters of alanine, pyruvate or lactate metabolism (Table 1).”
- Also stated in: § Discussion · plain
“GH administration did not influence any parameter of lactate metabolism.”
Quote in the paperNot a substantial claim - Also stated in: § Discussion · plain
- Premisecitation
Pituitary and recombinant human growth hormone have identical metabolic effects in man.
“Pituitary and recombinant human GH have been shown to have identical metabolic effects in man [20].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Rosenfeld RG, Wilson DM, Dollar LA, Bennett A, Hintz RL (1982) Both human pituitary growth hormone and recombinant DNA-derived human growth hormone cause insulin resistance at a postreceptor site. J Clin Endocrinol Metab 54: 1033?1038 source
Not checked in the free run.
- Interpretationown data
The present data confirm that the major tissue where growth hormone impairs insulin sensitivity to glucose utilisation is skeletal muscle.
“The present data confirm that the major tissue where GH impairs insulin sensitivity to glucose utilisation is skeletal muscle; tracer determined glucose disposal was decreased by 10% and the M-value by 38%; whereas glucose uptake by the forearm was decreased by 58%.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
- The authors state this as an assumption: Red cell intracellular NEFA equilibrate freely with plasma NEFA, and total blood concentration of NEFA can be calculated by multiplying plasma NEFA by (1 - 0.30 × hematocrit).
- The authors state this as an assumption: When catabolised oxidatively, ATP production from one mole of glucose, 3-hydroxybutyrate and NEFA (palmitate) is 38, 30 and 129 moles of ATP respectively.
- Interpretationown data
With growth hormone, the M-value started to decrease at least 1 h earlier.
“With GH, the M-value started to decrease at least 1 h earlier (Fig. 2).”
Quote in the paperSubstantial claim - Interpretationreasoning
The observed changes in lipid intermediates are unlikely to play any role in the early impairment of glucose sensitivity to insulin.
“As the observed changes in lipid intermediates are unlikely to play any role in the early impairment of glu-109 cose sensitivity to insulin”
Quote in the paperSubstantial claim - Interpretationown data
Growth hormone overcomes the anti-lipolytic effects of moderate hyperinsulinaemia.
“Our results demonstrate that GH does overcome the anti-lipolytic effects of moderate hyperinsulinaemia.”
Quote in the paperSubstantial claim - Interpretationcitation
The decrease in tracer determined disposal is possibly an underestimate of the true events because the tracer requires time to equilibrate with glucose compartments in the body.
“It is possible that the decrease in tracer determined disposal is an underestimate of the true events since, with changes in turnover, the tracer requires some time to equilibrate with glucose compartments in the body [32].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] Ferrannini E, Smith JD, Cobelli C, Toffolo G, Pilo A, DeFronzo RA (1985) Effect of insulin on the distribution and disposition of glucose in man. J Clin Invest 76: 357?364 source
Not checked in the free run.
- Interpretationreasoning
Modulation of post-receptor events (i.e. enzymes) represents the most likely mechanism whereby growth hormone acutely impairs glucose disposal.
“As the observed changes in lipid intermediates are unlikely to play any role in the early impairment of glu-109 cose sensitivity to insulin and as short term infusion of GH has been shown not to interfer with insulin receptor binding [3,4], modulation of post-receptor events (i.e. enzymes) represents the most likely mechanism, whereby GH acutely impairs glucose disposal.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [3] Bratusch-Marrain PR, Smith D, DeFronzo RA (1982) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973?982 source
Not checked in the free run.
- cites [4] Rizza R, Mandarino LW, Gerich JE (1982) Effects of growth hormone on insulin action in man. Diabetes 31: 663?669 source
Not checked in the free run.
- Premisecitation
Short term infusion of growth hormone has been shown not to interfere with insulin receptor binding.
“short term infusion of GH has been shown not to interfer with insulin receptor binding [3,4]”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [3] Bratusch-Marrain PR, Smith D, DeFronzo RA (1982) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973?982 source
Not checked in the free run.
- cites [4] Rizza R, Mandarino LW, Gerich JE (1982) Effects of growth hormone on insulin action in man. Diabetes 31: 663?669 source
Not checked in the free run.
- Premisecitation
Most reports have shown that in man exogenous growth hormone augments lipolysis.
“Most [9,10], but not all [3] reports, have shown that in man exogenous GH augments lipolysis”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [9] Fineberg SE, Merimee TJ (1974) Acute metabolic effects of human growth hormone. Diabetes 23: 499?504 source
Not checked in the free run.
- cites [10] Sherwin RS, Schulman GA, Hendler R, Walesky M, Belous A, Tamborlane W (1983) Effect of growth hormone on oral glucose tolerance and circulating metabolic fuels in man. Diabetologia 24: 155?161 source
Not checked in the free run.
- cites [3] Bratusch-Marrain PR, Smith D, DeFronzo RA (1982) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973?982 source
Not checked in the free run.
- Interpretationown data
The early effects of growth hormone on glucose metabolism seem independent of changes in the rate of lipolysis.
“The early effects of growth hormone on glucose metabolism seems independent of changes in the rate of lipolysis.”
Quote in the paperSubstantial claim - Premisecitation
During a conventional hyperinsulinaemic euglycemic clamp, the major fate of glucose taken up by muscle tissue is non-oxidative conversion into glycogen.
“During a conventional hyperinsulinaemic euglycemic clamp, the major fate of the glucose taken up by muscle tissue is non-oxidative conversion into glycogen [31,33];”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [31] DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP (1981) The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catherization. Diabetes 30: 1000?1007 source
Not checked in the free run.
- cites [33] Bogardus C, Lillioja S, Stone K, Mott D (1984) Correlation between muscle glycogen synthase activity and in vivo insulin action in man. J Clin Invest 73: 1185?1190 source
Not checked in the free run.
- Interpretationown data
Growth hormone has independent actions to decrease peripheral (i.e. muscular) glucose uptake.
“Unless GH induces an increase in local or intra-myocytic release and utilisation of NEFA, our data strongly suggests that GH has independent actions to decrease peripheral (i.e. muscular) glucose uptake.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
- The authors state this as an assumption: Red cell intracellular NEFA equilibrate freely with plasma NEFA, and total blood concentration of NEFA can be calculated by multiplying plasma NEFA by (1 - 0.30 × hematocrit).
- The authors state this as an assumption: When catabolised oxidatively, ATP production from one mole of glucose, 3-hydroxybutyrate and NEFA (palmitate) is 38, 30 and 129 moles of ATP respectively.
- Premisecitation
Sustained elevation of growth hormone levels is associated with a decrease in glucose sensitivity to insulin, both in the liver and in extrahepatic tissues.
“Studies in patients with acromegaly [2] and in normal [3,4] and diabetic [5] man given GH for various periods of time have shown that sustained elevation of GH-levels is associated with a decrease in glucose sensitivity to insulin, both in the liver and in extrahepatic tissues.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [2] Hansen I, Tsalikian E, Beaufrere B, Gerich J, Raymond M, Rizza R (1986) Insulin resistance in acromegaly: defects in both hepatic and extrahepatic insulin action. Am J Physiol 250: E269-E273
Not checked in the free run.
- cites [3] Bratusch-Marrain PR, Smith D, DeFronzo RA (1982) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973?982 source
Not checked in the free run.
- cites [4] Rizza R, Mandarino LW, Gerich JE (1982) Effects of growth hormone on insulin action in man. Diabetes 31: 663?669 source
Not checked in the free run.
- cites [5] Press M, Tamborlane MW, Sherwin RS (1984) Importance of raised growth hormone levels in mediating the metabolic derangements of diabetes. N Engl J Med 310: 810?815 source
Not checked in the free run.
- Interpretationnone given
Only with more sustained elevations of growth hormone, as seen in many pathological states, is the glucose/fatty acid/ketone body cycle likely to achieve increasing significance in the pathogenesis of peripheral insulin insensitivity.
“Only with more sustained elevations of GH, as seen in many pathological states, is the glucose/fatty acid/ketone body cycle likely to achieve increasing significance in the pathogenesis of peripheral insulin insensitivity.”
Quote in the paperNot a substantial claim - Interpretationown data
The present data show that, with modest hyperinsulinaemia, overall insulin sensitivity as judged by the M-value is diminished after 3 h.
“The present data show that, with modest levels of hyperinsulinaemia, overall insulin sensitivity as judged by the M-value is diminished after 3 h.”
Quote in the paperSubstantial claim - Interpretationcitation
In the physiological state, the insulin agonistic action of growth hormone is probably the more important.
“In the physiological state, the insulin agonistic action of GH is probably the more important, since significant secretion of GH and insulin very rarely coincides and since secretory bursts of GH are usually shortlived [29].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Parker DC, Rossman LG, Kripke DF, Gibson W, Wilson K (1979) In: Krieger DT (ed) Endocrine Rhythms. Raven Press, New York, pp 143?175
Not checked in the free run.
- May combine two claims. 19
- Classified as probably not a substantial claim. 12
May combine two claims.
Findingown dataInsulin infusion caused the glucose infusion rate (M-value) to increase to 4.4 ± 0.3 mg/kg/min, glucose disposal rate (Rd) to rise to 4.0 ± 0.2 mg/kg/min, and hepatic glucose output (HGO) to decrease to -0.4 ± 0.2 mg/kg/min at 240 min.
“As shown in Figure 2, insulin infusion caused the glucose infusion rate (M-value) to increase steadily to 4.4 + 0.3 mg.kg-1.min-1 at 240 min, the disposal rate for glucose (Rd) to rise to a maximum of 4.0+0.2mg-kg -1 -rain -1 at 240 min and HGO to decrease, therefore, to -0.4+0.2 mg-kg -1-min -1 at 240 min.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataGrowth hormone caused hepatic glucose output to rise to 0.7 ± 0.2 mg/kg/min at 240 min (p < 0.05); this effect on glucose production was significant after 120 min.
“GH caused HGO to rise to 0.7_+0.2mg.kg-l-min-t at 240min (p < 0.05); this effect on glucose production was significant after 120 min.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataTotal forearm blood flow did not change in any of the studies but remained constant around a baseline value of 2.4 ± 0.2 ml/100 ml/min.
“Total forearm blood flow did not change in any of the studies but remained constant around a baseline value of 2.4 + 0.2 ml/100 ml/min.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
May combine two claims.
Findingown dataWhen growth hormone was added, plasma NEFA, blood glycerol and 3-hydroxybutyrate rose towards the end of the study, achieving maximum values at 240 min of 480 ± 60 (p < 0.05), 43 ± 6 (p < 0.01) and 30 ± 3 (p < 0.05) μmol/l respectively.
“When GH was added, all three metabolites rose towards the end of the study period achieving maximum values of 480_+ 60 (p < 0.05), 43 _+ 6 (p < 0.01) and 30 + 3 (p < 0.05) ~tmol/1 respectively at 240 min.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataOnly at 240 min was forearm uptake of 3-hydroxybutyrate significantly increased with growth hormone; forearm uptake of NEFA was not affected by growth hormone at any timepoint.
“Only at 240 min was the forearm uptake of 3-hydroxybutyrate significantly increased; whereas uptake of NEFA was not affected by GH at any timepoint.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
- The authors state this as an assumption: Red cell intracellular NEFA equilibrate freely with plasma NEFA, and total blood concentration of NEFA can be calculated by multiplying plasma NEFA by (1 - 0.30 × hematocrit).
- The authors state this as an assumption: When catabolised oxidatively, ATP production from one mole of glucose, 3-hydroxybutyrate and NEFA (palmitate) is 38, 30 and 129 moles of ATP respectively.
May combine two claims.
Findingown dataInsulin infusion caused serum insulin to rise from 4 ± 1 mU/l to a plateau of 15 ± 1 mU/l and serum C-peptide to drop from 0.40 ± 5 nmol/l to 0.21 ± 4 nmol/l (p < 0.01).
“Infusion of insulin caused serum insulin to rise from 4+1 mU/1 to a plateau of 15+1 mU/1 and serum Cpeptide to drop from a baseline level of 0.40_+ 5 nmol/1 to 0.21 _+ 4 nmol/1 (p < 0.01) (Fig. 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataGrowth hormone administration did not affect serum insulin or C-peptide.
“Introduction of GH did not affect either parameters.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe decrements in M-value and Rd achieved significance after 180 and 225 min of growth hormone administration.
“These decrements achieved significance after 180 and 225 rain of GH administration.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataGrowth hormone administration diminished the M-value by 36% (2.8 ± 0.2 mg/kg/min at 240 min, p < 0.05) and Rd by 10% (3.6 ± 0.2 mg/kg/min at 240 min).
“GH administration diminished the M-value by 36% (2.8_+0.2mg.kg-l-min-1 at 240min, p<0.05) and Rd by 10% (3.6_+0.2mg.kg-l-min -1 at 240 min”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe increases in NEFA, glycerol and 3-hydroxybutyrate with growth hormone were statistically significant from 210 min, 180 min and 240 min respectively, compared to insulin administration alone.
“The increases of these values were statistically significant from 210min (NEFA), 180min (glycerol) and 240 min (3-hydroxybutyrate), when compared to insulin administration alone.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataGrowth hormone caused glucose uptake to decrease and uptake of lipid substrates to increase across deep forearm tissues; total uptake of ATP equivalents was decreased with growth hormone.
“GH caused glucose uptake to decrease and uptake of lipid substrates to increase.Total uptake of ATP equivalents was decreased with GH.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
- The authors state this as an assumption: Red cell intracellular NEFA equilibrate freely with plasma NEFA, and total blood concentration of NEFA can be calculated by multiplying plasma NEFA by (1 - 0.30 × hematocrit).
- The authors state this as an assumption: When catabolised oxidatively, ATP production from one mole of glucose, 3-hydroxybutyrate and NEFA (palmitate) is 38, 30 and 129 moles of ATP respectively.
Classified as probably not a substantial claim.
Study design and conductcitationBlood glucose was clamped at a value 0.2 mmol/l below fasting level to minimise fluctuations in endogenous insulin secretion.
“the blood glucose was clamped at a value 0.2 mmol/1 below fasting level (to minimise fluctuations in endogenous insulin secretion) by adjusting a variable infusion of 20% glucose [19].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and insulin resistance. Am J Physiol 237: E214-E224
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationForearm studies have suggested that growth hormone acutely decreases peripheral disposal of glucose.
“whereas forearm studies have suggested that GH acutely decreases peripheral disposal of glucose [8,9].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [8] Rabinowitz D, Klassen GA, Zierler KL (1965) Effect of human growth hormone on muscle and adipose tissue metabolism in the forearm of man. J Clin Invest 44: 51?61 source
Not checked in the free run.
- cites [9] Fineberg SE, Merimee TJ (1974) Acute metabolic effects of human growth hormone. Diabetes 23: 499?504 source
Not checked in the free run.
May combine two claims.
Interpretationown dataThe tracer data indicate that hepatic insulin sensitivity is affected after 2 h and extrahepatic sensitivity after 3.5 h of growth hormone exposure.
“The tracer data indicate that hepatic insulin sensitivity is affected after 2 h and extrahepatic sensitivity after 3.5 h of GH exposure.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisenone givenThe length of time for growth hormone to exert these actions has not been precisely determined.
“The length of time for GH to exert these actions has not been precisely determined.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningWith the more moderate insulin dose employed in the present study, muscular glucose oxidation may be of equal importance, and growth hormone could thus inhibit oxidative as well as non-oxidative utilisation of glucose in muscle.
“with the more moderate insulin dose employed in the present study, muscular glucose oxidation may, however, be of equal importance, and GH could thus inhibit oxidative as well as non-oxidative utilisation of glucose in muscle.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenTwo hours were allowed for the isotope to equilibrate.
“Two hours were allowed for the isotope to equilibrate.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenIn each individual, the same veins were used for catheter insertion on each occasion.
“In each individual, the same veins were used for insertion on each occasion.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataGrowth hormone acts as a partial insulin agonist on the liver: it suppresses hepatic glucose output in the postabsorptive state and increases hepatic glucose output in the presence of hyperinsulinaemia.
“It is of interest that GH apparently acts as a partial insulin agonist on the liver, i.e. suppresses HGO in the postabsorptive state and increases HGO in the presence of hyperinsulinaemia.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn the basal state, growth hormone administration induces an early insulin-like effect on glucose metabolism.
“earlier studies indicated that in the basal state, GH administration induces an early insulin-like effect on glucose metabolism [6,7]”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [6] Adamson U, Wahren J, Cerasi E (1977) Influence of growth hormone on splanchnic glucose production in man. Acta Endocrinol 86: 803?812 source
Not checked in the free run.
- cites [7] MacGorman LR, Rizza RA, Gerich JE (1981) Physiological concentrations of growth hormone exert insulin-like and insulin antagonistic effects on both hepatic and extrahepatic tissues in man. J Clin Endocrinol Metab 53: 556?559 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe failure of one study [3] to demonstrate insulin insensitivity after 2 h could relate to the higher dose of insulin employed.
“The failure of one of the above studies [3] to demonstrate insulin insensitivity after 2 h could relate to the higher dose of insulin employed.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] Bratusch-Marrain PR, Smith D, DeFronzo RA (1982) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973?982 source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductcitationThe criteria for satisfactory positioning of the deep antecubital vein catheter were that the tip could not be palpated and that oxygen saturation in blood drawn from the catheter was below 60%.
“that the tip of the catheter could not be palpated, and that the oxygen saturation in blood drawn from the catheter was below 60% [13].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Wahren J (1966) Quantitative aspects of blood flow and oxygen uptake in the human forearm during rhythmic exercise. Acta Physiol Scand 67 [Suppl 269]: 1?93
Not checked in the free run.
May combine two claims.
Interpretationown dataThese data suggest that growth hormone induces insensitivity to insulin in liver, muscle and fat after 120, 180 and 210 min respectively.
“These data suggest that growth hormone induces insensitivity to insulin in liver, muscle and fat after 120, 180 and 210 min respectively.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationThere is evidence that growth hormone increases the fraction of non-esterified fatty acids being oxidised to ketone bodies in the liver.
“there is evidence to support that GH increases the fraction of non-esterified fatty acids (NEFA) being oxidised to ketone bodies in the liver [11].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Keller U, Schell H, Girard J, Stauffacher W (1984) Effect of physiological elevation of plasma growth hormone levels on ketone body kinetics and lipolysis in normal and acutely insulin-deficient man. Diabetologia 26: 103?108 source
Not checked in the free run.
May combine two claims.
Interpretationown dataThe early increase in circulating lactate was due to a release from tissues other than muscle or a decrease in clearance.
“No consistent forearm release of lactate was recorded until 3 h into the clamp, suggesting that the early increase in circulating lactate was due to a release form tissues other than muscle or a decrease in clearance.”
Quote in the paperNot a substantial claim- The authors state this as an assumption: The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenOxygen saturation in blood drawn from the heated dorsal hand vein was consistently above 91%.
“Oxygen saturation in blood drawn from the heated dorsal hand vein was consistently above 91%.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningThe inconsistency in results compared to the previous study [3] could relate to the more moderate insulin dose given and the longer clamp-period in the present study.
“Again the inconsistency in results compared to the previous study [3] could relate to the more moderate insulin dose given and the longer clamp-period in the present study.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] Bratusch-Marrain PR, Smith D, DeFronzo RA (1982) The effect of growth hormone on glucose metabolism and insulin secretion in man. J Clin Endocrinol Metab 55: 973?982 source
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductnone givenSubjects were studied on two occasions in random order and with minimum intervals of 4 weeks.
“Subjects were studied on 2 occasions in random order and with minimum intervals of 4 weeks: (1) receiving a 6 h i.v.infusion of insulin (euglycemic clamp); (2) receiving an insulin infusion (6 h) together with a GH infusion (4 h).”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductreasoningThe tracer data should be interpreted with caution because inadequacy of the isotope dilution technique may lead to under-estimation of hepatic glucose output and inability to detect small changes in glucose turnover.
“These data should, however, be interpreted with some caution since inadequacy of the isotope dilution technique in its present form, whether caused by a non-steady state error or by isotope discrimination/contamination, may lead to under-estimation of HGO and inability to detect small changes in glucose turnover.”
Quote in the paperSubstantial claim
The authors state this as an assumption.
The relative blood flow to the tissues drained by the deep forearm vein equals 0.47 times total forearm blood flow plus 0.83.
“The relative blood flow (ml/100 ml/min) to the tissues drained by the deep forearm vein equals 0.47 x total forearm blood flow+0.83[16].”
The authors state this as an assumption.
Red cell intracellular NEFA equilibrate freely with plasma NEFA, and total blood concentration of NEFA can be calculated by multiplying plasma NEFA by (1 - 0.30 × hematocrit).
“Red cell intracellular NEFA equilibrate freely with plasma NEFA and total blood concentration of NEFA can thus be calculated by multiplying plasma NEFA by (1-0.30x hematocrit) (similar to the way in which plasma glucose values are converted to whole blood glucose values [17]).”
The authors state this as an assumption.
When catabolised oxidatively, ATP production from one mole of glucose, 3-hydroxybutyrate and NEFA (palmitate) is 38, 30 and 129 moles of ATP respectively.
“When being catabolised oxidatively the ATP production from one mol of glucose, 3-hydroxybutyrate and NEFA (i.e.palmitate) is 38, 30 and 129 mol of ATP respectively [18].”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
GHRH injection increased glucose levels at awakening by almost 50% and growth hormone administration rapidly decreased muscular glucose uptake.
“GHRH injection increased glucose levels at awakening by almost 50%56 and GH administration rapidly decreased muscular glucose uptake.55,57”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [57]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Forearm glucose uptake did not decline before every detectable lipid increase
MajorThe paper says forearm glucose uptake decreased significantly after 180 minutes of GH administration, but also says circulating glycerol increased significantly from 180 minutes. Those reported onsets are simultaneous, not sequential as the abstract claims.
“The decrease in forearm glucose uptake and glucose infusion rate and the increase in hepatic glucose production was observed before there was any detectable increase in circulating levels and forearm uptake of lipid intermediates.”
“The increases of these values were statistically significant from 210min (NEFA), 180min (glycerol) and 240 min (3-hydroxybutyrate), when compared to insulin administration alone.”
ATP-equivalent table values are labeled in the wrong units
MinorThe stated glucose uptake of 2340 nmol/100 ml/min, multiplied by the stated yield of 38 ATP per glucose, gives 88,920 nmol, or 0.08892 mmol, of ATP equivalents. The table reports 88.9 under a mmol/100 ml/min heading-a value consistent with μmol, not mmol.
Reported 88.9 · recomputed 88920
“| Glucose | 4.41 +-0.14 | 370_+_ 40 | 14.1+1.5 | 4.22_+0.11 | 2340_+480 88.9+_18.2 | 4.17_+0.14 | 1060+170 a 40.3_+6.5 a | | |”
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“[7] have suggested that GH, in the basal state, exerts an acute insulin agonistic effect on the liver and hepatic venous catheterisation has indicated that administration of pharmacological GH doses decreases splanchnic glucose output by 35-40% in man [6].”
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“[7] have suggested that GH, in the basal state, exerts an acute insulin agonistic effect on the liver and hepatic venous catheterisation has indicated that administration of pharmacological GH doses decreases splanchnic glucose output by 35-40% in man [6].”
BackgroundResult
Flagged first, then by citations
Research works printed but not linked: 1
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Cited by
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Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-α,in Vivo1
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Self-citationRoles of Circadian Rhythmicity and Sleep in Human Glucose Regulation
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“Since there is a few hours lag before growth hormone exerts its insulinantagonistic effects [97], the resulting insulin resistance occurs in the early morning hours and coincides with the rise in cortisol levels at that time [98].”
BackgroundThe effect of altitude hypoxia on glucose homeostasis in men
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Self-citationA review of cancer cachexia and abnormal glucose metabolism in humans with cancer.
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Self-citationInternal desynchronization in a model of night-work by forced activity in rats
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Pharmacological Antilipolysis Restores Insulin Sensitivity During Growth Hormone Exposure
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Self-citationNormal basal and insulin-stimulated fuel metabolism in lean women with the polycystic ovary syndrome
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“In the left arm, blood sampling cannulas were inserted into an anticubital vein draining deep forearm tissues (16) and into the radial artery for A-V measurements.”
The metabolic role of growth hormone in humans with particular reference to fasting
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“It has, however, also been reported that GH-induced insulin resistance preceded the increase in circulating concentrations and forearm uptake of lipid intermediates [152].”
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Growth Hormone and Glucose Homeostasis
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“(fig. 1 ). It has, however, also been reported that GH-induced insulin resistance preceded the increase in circulating levels and forearm uptake of lipid intermediates [”
BackgroundSelf-citationKrag, M. B., Gormsen, L. C., Guo, Z., Christiansen, J. S., Jensen, M. D., Nielsen, S., & Jørgensen, J. O. L. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00374.2006 · Cited by 101 · see citing works
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“GH has insulin antagonistic effects with respect to glucose and lipid metabolism, as it increases hepatic glucose production, decreases peripheral glucose utilization (8, 9), and increases lipolysis (10).”
BackgroundEffect of growth hormone on insulin signaling
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Self-citationEffects of growth hormone on lipid metabolism in humans
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“Following administration of more moderate amounts of both GH and insulin, it was observed that: GH impaired hepatic and peripheral insulin sensitivity after approximately 2 h; impairment of peripheral insulin sensitivity largely resided in muscle; and GH had the potency to offset the antilipolytic actions of light hyp…”
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“Sustained elevation of GH levels results in decreased insulin sensitivity at the liver and in peripheral tissues (27, 28).”
BackgroundNørrelund, H., Wiggers, H., Halbirk, M., Frystyk, J., Flyvbjerg, A., Bøtker, H. E., Schmitz, O., Jørgensen, J. O. L., Christiansen, J. S., & Møller, N. (2006) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2006.01663.x · Cited by 80 · see citing works
Self-citationThe influence of sleep and sleep loss upon food intake and metabolism
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Self-citationImpact of successful transsphenoidal surgery on cardiovascular risk factors in acromegaly
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Self-citationEffects of Growth Hormone on Glucose and Fat Metabolism in Human Subjects
Jørgensen, J. O. L., Møller, L. F., Krag, M. B., Billestrup, N., & Christiansen, J. S. (2007) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2006.11.005 · Cited by 72 · see citing works
Wang, Z., & Olumi, A. F. (2011) · Differentiation · doi:10.1016/j.diff.2011.04.004 · Cited by 73 · see citing works
Jørgensen, J. O. L., Jessen, N., Pedersen, S. B., Vestergaard, E. T., Gormsen, L. C., Lund, S. A., & Billestrup, N. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00024.2006 · Cited by 73 · see citing works
“GH acutely antagonizes insulin-stimulated glucose uptake in skeletal muscle, as shown originally by Zierler and Rabinowitz (23) and in a number of studies using the euglycemic hyperinsulinemic glucose clamp technique (3, 16, 18, 22).”
MethodBak, J. F., Møller, N., Schmitz, O., Saaek, A., & Pedersen, O. B. (1992) · Diabetologia · doi:10.1007/bf00429100 · Cited by 72 · see citing works
Self-citationJørgensen, J. O. L., Pedersen, S. B., Børglum, J. D., Møller, N., Schmitz, O., Christiansen, J. S., & Richelsen, B. (1994) · Metabolism · doi:10.1016/0026-0495(94)90269-0 · Cited by 71 · see citing works
Self-citationRiis, A. L. D., Jørgensen, J. O. L., Gjedde, S., Nørrelund, H., Jurik, A. G., Nair, K. S., Ivarsen, P., Weeke, J., & Møller, N. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00253.2004 · Cited by 71 · see citing works
“One intravenous catheter (Viggo, Helsingborg, Sweden) was placed in an antecubital vein for infusions, another in the contralateral antecubital vein for deep venous samples, and a third in a superficial vein draining the ipsilateral hand, which was heated in a box with an air temperature of 65°C to provide arterialize…”
MethodSelf-citationChild, C. J., Zimmermann, A. G., Scott, R. S., Cutler, G. B., Battelino, T., & Blum, W. F. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-3023 · Cited by 71 · see citing works
Metabolic actions of growth hormone: direct and indirect
Berneis, K. K., & Keller, U. B. (1996) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(96)80470-8 · Cited by 70 · see citing works
Recombinant growth hormone treatment of amyotrophic lateral sclerosis
Smith, R. A., Melmed, S. K., Sherman, B. M., France, J., Munsat, T. L., & Festoff, B. W. (1993) · Muscle & Nerve · doi:10.1002/mus.880160608 · Cited by 70 · see citing works
Ho, K. K. Y., Jenkins, A. B., Furler, S. M., Borkman, M., & Chisholm, D. J. (1992) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1992.tb01443.x · Cited by 68 · see citing works
Cauter, E. V., Polonsky, K. S., Blackman, J. D., Roland, D., Sturis, J., Byrne, M. M., & Scheen, A. J. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.6.7989487 · Cited by 69 · see citing works
Jessen, N., Djurhuus, C., Jørgensen, J. O. L., Jensen, L. S., Møller, N., Lund, S. A., & Schmitz, O. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00149.2004 · Cited by 66 · see citing works
Self-citationTwenty-four-hour rhythms of plasma glucose and insulin secretion rate in regular night workers
Simon, C., Weibel, L., & BRANDENBERGER, G. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.278.3.e413 · Cited by 62 · see citing works
Nielsen, C., Gormsen, L. C., Jessen, N., Pedersen, S. B., Møller, N., Lund, S. A., & Jørgensen, J. O. L. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2414 · Cited by 63 · see citing works
“The metabolic effects are complex and depend in part onsubstrateavailability.Inthepostabsorptivephaseandduring fasting,GHpromoteslipolysisandlipidoxidationattheexpense of glucose oxidation (1, 2 ). If these effects operate postprandially, which is the case in active acromegaly and during sc GH administration,insulinre…”
BackgroundSelf-citationCotreatment with Pegvisomant and a Somatostatin Analog (SA) in SA-Responsive Acromegalic Patients
Madsen, M. A., Poulsen, P. L., Ørskov, H., Møller, N., & Jørgensen, J. O. L. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0654 · Cited by 60 · see citing works
Self-citationGlucose and Lipid Fluxes in the Adipose Tissue after Meal Ingestion in Hyperthyroidism
Dimitriadis, G., Mitrou, P., Lambadiari, V., Boutati, E. I., Maratou, E., Koukkou, E., Tzanela, M., Thalassinos, N., & Raptis, S. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0960 · Cited by 60 · see citing works
Metabolic effects of growth hormone in humans
Møller, N., Jørgensen, J. O. L., Møller, J., Ørskov, L., Ovesen, P., Schmitz, O., Christiansen, J. S., & Ørskov, H. (1995) · Metabolism · doi:10.1016/0026-0495(95)90218-x · Cited by 59 · see citing works
Self-citationNormal splanchnic but impaired peripheral insulin-stimulated glucose uptake in cirrhosis
Shmueli, E., Walker, M., Alberti, G., & Record, C. O. (1993) · Hepatology · doi:10.1002/hep.1840180115 · Cited by 56 · see citing works
No Evidence of Ectopic Lipid Accumulation in the Pathophysiology of the Acromegalic Cardiomyopathy
Winhofer, Y., Wolf, P. S., Krššák, M., Wolfsberger, S., Tura, A., Pacini, G., Gessl, A., Raber, W., Kukurová, I. J., Kautzky‐Willer, A., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2242 · Cited by 56 · see citing works
Effects of pulsatile delivery of basal growth hormone on lipolysis in humans
Cersósimo, E., Danou, F. N., Persson, M., & Miles, J. M. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.271.1.e123 · Cited by 55 · see citing works
Salgin, B., Marcovecchio, M. L., Humphreys, S. M., Hill, N. R., Chassin, L. J., Lunn, D. J., Hovorka, R., & Dunger, D. B. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90613.2008 · Cited by 52 · see citing works
“This was associated with increases in mean GH levels, independent of changes in FFA levels, which may signify a direct effect of elevated GH levels on SI (32, 33, 46).”
BackgroundMechanism of growth hormone-induced postprandial carbohydrate intolerance in humans
Butler, P. C., Kryshak, E. J., & Rizza, R. A. (1991) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1991.260.4.e513 · Cited by 51 · see citing works
Self-citationNellemann, B., Vendelbo, M. H., Nielsen, T. S., Bak, A. M., Høgild, M. L., Pedersen, S. B., Biensø, R. S., Pilegaard, H., Møller, N., Jessen, N., et al. (2013) · Acta Physiologica · doi:10.1111/apha.12183 · Cited by 51 · see citing works
“The specific activity (SA) of [3-(3)H]glucose was measured as previously described (Moller et al. 1989).”
MethodSelf-citationKrusenstjerna-Hafstrøm, T., Clasen, B. F., Møller, N., Jessen, N., Pedersen, S. B., Christiansen, J. S., & Jørgensen, J. O. L. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-0273 · Cited by 49 · see citing works
Self-citationImpact of Fasting on Growth Hormone Signaling and Action in Muscle and Fat
Møller, L. F., Dalman, L., Nørrelund, H., Billestrup, N., Frystyk, J., Møller, N., & Jørgensen, J. O. L. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1385 · Cited by 48 · see citing works
Self-citationBak, A. M., Møller, A. B., Vendelbo, M. H., Nielsen, T. S., Viggers, R., Rungby, J., Pedersen, S. B., Jørgensen, J. O. L., Jessen, N., & Møller, N. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00464.2015 · Cited by 49 · see citing works
Self-citationGhrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep
Takahashi, H., Kurose, Y., Kobayashi, S., et al. (2006) · Journal of Endocrinology · doi:10.1677/joe.1.06310 · Cited by 46 · see citing works
“Furthermore, acute and chronic elevations of blood GH levels cause insulin resistance (Rizza et al. 1982, Moller et al. 1989, Hettiarachchi et al. 1996, Kim et al. 1999).”
BackgroundPeriprandial regulation of lipid metabolism in insulin-treated diabetes mellitus
Frayn, K. N., Coppack, S. W., Humphreys, S. M., Clark, M. L., & Evans, R. D. (1993) · Metabolism · doi:10.1016/0026-0495(93)90110-a · Cited by 45 · see citing works
HYPERGLYCEMIC CRISES IN DIABETES MELLITUS TYPE 2
Trence, D., & Hirsch, I. B. (2001) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70217-6 · Cited by 42 · see citing works
Meller, N., Møller, J., Jørgensen, J. O. L., Ovesen, P., Schmitz, O., Albert, K. G. M. M., & Christiansen, J. S. (1993) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1993.tb02412.x · Cited by 42 · see citing works
Baroni, M. G., Giorgino, F., Pezzino, V., Scaroni, C., & Avogaro, A. (2016) · Journal of Endocrinological Investigation · doi:10.1007/s40618-015-0404-6 · Cited by 41 · see citing works
“When GH is present in excess, both acute and chronic GH exposure induces insulin resistance by increasing endogenous glucose production and decreasing peripheral glucose disposal in muscle [22, 23].”
BackgroundStøy, J., Kampmann, U., Mengel, A., Magnusson, N. E., Jessen, N., Grarup, N., Rungby, J., Stødkilde‐Jørgensen, H., Brandslund, I., Christensen, C., et al. (2015) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2015-000095 · Cited by 41 · see citing works
Self-citationAcyl Ghrelin Induces Insulin Resistance Independently of GH, Cortisol, and Free Fatty Acids
Vestergaard, E. T., Jessen, N., Møller, N., & Jørgensen, J. O. L. (2017) · Scientific Reports · doi:10.1038/srep42706 · Cited by 41 · see citing works
Self-citationGjedsted, J., Gormsen, L. C., Nielsen, S., Schmitz, O., Djurhuus, C., Keiding, S., Ørskov, H., Tønnesen, E., & Møller, N. (2007) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01740.x · Cited by 41 · see citing works
“Intravenous catheters (Viggo, Helsingborg, Sweden) were placed in an antecubital vein for infusions, and in a retrograde manner in the contralateral antecubital vein for deep venous samples, arterial blood was sampled from the femoral artery (Moller et al. 1989).”
MethodSelf-citation1 Liver disease, carbohydrate metabolism and diabetes
Shmueli, E., Record, C. O., & Alberti, K. G. M. M. (1992) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(05)80163-6 · Cited by 40 · see citing works
Self-citationGrowth hormone and lean tissue catabolism during long‐term glucocorticoid treatment
Bennet, W. M., & Haymond, M. W. (1992) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1992.tb00951.x · Cited by 40 · see citing works
Nørrelund, H., Djurhuus, C., Jørgensen, J. O. L., Nielsen, S., Nair, K. S., Schmitz, O., Christiansen, J. S., & Møller, N. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00092.2003 · Cited by 39 · see citing works
“More sustained exposure to high GH levels has been shown to induce both peripheral and hepatic insulin resistance (5, 11, 23, 38).”
BackgroundSelf-citationEffects of aging on glucose regulation during wakefulness and sleep
Frank, S. A., Roland, D. C., Sturis, J., Byrne, M. M., Refetoff, S., Polonsky, K. S., & Cauter, E. V. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.269.6.e1006 · Cited by 38 · see citing works
Mediation of the Hepatic Effects of Growth Hormone by Its Lipolytic Activity
Piatti, P., Monti, L. D., Caumo, A., Conti, M., Magni, F., Galli-Kienle, M., Fochesato, E., Pizzini, A., Baldi, L., Valsecchi, G., et al. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.5.5685 · Cited by 41 · see citing works
Acute exposure to GH during exercise stimulates the turnover of free fatty acids in GH-deficient men
Kanaley, J. A., Dall, R., Møller, N., Nielsen, S. C., Christiansen, J. S., Jensen, M. D., & Jørgensen, J. O. L. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00711.2003 · Cited by 38 · see citing works
“In contrast, GH is found to inhibit peripheral glucose clearance after 2–3 h during hyperinsulinemic euglycemic clamps (22), indicating that GH inhibition of muscle glucose uptake plays a quantitatively far more important role during hyperinsulinemia.”
BackgroundMethodSelf-citationStewart, T. A., Clift, S., Pitts-Meek, S., Martin, L., Terrell, T. G., Liggitt, D., & Oakley, H. (1992) · Endocrinology · doi:10.1210/endo.130.1.1727714 · Cited by 37 · see citing works
Nørrelund, H., Nielsen, S., Christiansen, J., Jørgensen, J. O. L., & Møller, N. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.1500779 · Cited by 33 · see citing works
“Several studies have shown that GH postabsorptively antagonises the effects of insulin on glucose and lipid metabolism (4, 9, 26 ).”
BackgroundSelf-citationYuen, K. C. J., Ong, K. K., Husbands, S., Chatelain, P., Fryklund, L., Gluckman, P. D., Ranke, M. B., Cook, D. M., Rosenfeld, R. G., Wass, J. A. H., et al. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.5.8460 · Cited by 34 · see citing works
Henriksen, J. E., Levin, K., Thye‐Rønn, P., ALFORD, F. P., Nielsen, O. H., Holst, J. J., & Beck‐Nielsen, H. (2000) · Diabetes · doi:10.2337/diabetes.49.7.1209 · Cited by 33 · see citing works
Impact of body composition on very-low-density lipoprotein-triglycerides kinetics
Gormsen, L. C., Nellemann, B., Sørensen, L. P., Jensen, M. D., Christiansen, J. S., & Nielsen, S. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90675.2008 · Cited by 32 · see citing works
M⊘ller, N., Blum, W. F., Mengel, A., et al. (1991) · Diabetologia · doi:10.1007/bf00404019 · Cited by 32 · see citing works
“In the "basal state" study forearm glucose uptake was measured [ 11 ].”
MethodSelf-citationOleksik, A. M., Duong, T., Pliester, N., Asma, G. B., Popp‐Snijders, C., & Lips, P. T. A. M. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.6.7549 · Cited by 33 · see citing works
Growth hormone, insulin-like growth factor-1 and insulin resistance in cirrhosis
Shmueli, E., Stewart, M. W., George, K., Alberti, M. M., & Record, C. O. (1994) · Hepatology · doi:10.1002/hep.1840190209 · Cited by 32 · see citing works
Body Composition Changes with Long-term Pegvisomant Therapy of Acromegaly
Kuker, A. P., Shen, W., Jin, Z., Singh, S., Chen, J., Bruce, J. N., & Freda, P. U. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab004 · Cited by 30 · see citing works
“In acromegaly and GH use, free fatty acids (FFA) flux and muscle uptake are increased [63-68] and in supraphysiologic GH increased IMCL on SM biopsy [69].”
BackgroundCiresi, A., Amato, M. C., & Giordano, C. S. D. S. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-014-0184-4 · Cited by 29 · see citing works
“GH treatment has therefore been suggested to impair glucose metabolism [9, 11, 12] and monitoring of glucose levels during GH treatment has been recommended in GHD subjects with diabetes mellitus risk factors because of the evidence of higher incidence of diabetes than the general population [13, 14].”
BackgroundRiis, A. L., Jørgensen, J. O. L., Ivarsen, P., Frystyk, J., Weeke, J., & Møller, N. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0550 · Cited by 27 · see citing works
“After regional catheterization (13), protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique with infusions of [(15)N]phenylalanine and [(2)H4]tyrosine and subsequent quantification of enrichment in plasma by gas chromatography mass spectrometry.”
MethodSelf-citationFreda, P. U. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.933039 · Cited by 28 · see citing works
Krusenstjerna-Hafstrøm, T., Madsen, M. A., Vendelbo, M. H., Pedersen, S. B., Christiansen, J. S., Møller, N., Jessen, N., & Jørgensen, J. O. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019392 · Cited by 27 · see citing works
“. In the post-absorptive phase, where endogenous GH secretion is stimulated, GH promotes lipolysis and oxidation of fatty acids at the expense of glucose”
Self-citationNutrient Uptake by the Hindlimb of Growing Pigs Treated with Porcine Somatotropin and Insulin
Wray‐Cahen, D., Bell, A. W., Boyd, R. D., Ross, D. A., Bauman, D. E., Krick, B. J., & Harrell, R. J. (1995) · Journal of Nutrition · doi:10.1093/jn/125.1.125 · Cited by 27 · see citing works
Growth hormone therapy in short children born small for gestational age
Ong, K. K., Beardsall, K., & de Zegher, F. (2005) · Early Human Development · doi:10.1016/j.earlhumdev.2005.10.010 · Cited by 26 · see citing works
“This is an expected consequence of its metabolic effects, as GH reduces glucose uptake into peripheral tissues [35] and by increasing lipolysis [36] it reduces insulin sensitivity [37,38].”
BackgroundMacdonald, I. A., Scott, A. R., Bowman, C. A., & Jeffcoate, W. J. (1990) · Diabetic Medicine · doi:10.1111/j.1464-5491.1990.tb01309.x · Cited by 26 · see citing works
Ørskov, L., Nyholm, B., Hove, K. Y., Gravholt, C. H., Møller, N., & Schmitz, O. (1999) · Diabetic Medicine · doi:10.1046/j.1464-5491.1999.00162.x · Cited by 25 · see citing works
Self-citationPeriprandial systemic and regional lipase activity in normal humans
Coppack, S. W., Yost, T. J., Fisher, R. M., Eckel, R. H., & Miles, J. M. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.4.e718 · Cited by 26 · see citing works
Glycerol and lactate uptake in human forearm
Frayn, K. N., Coppack, S. W., & Humphreys, S. M. (1991) · Metabolism · doi:10.1016/0026-0495(91)90035-u · Cited by 25 · see citing works
Dimitriadis, G., Parry‐Billings, M., Leighton, B., Piva, T. J., Dunger, D. B., Calder, P. C., BOND, J. A., & Newsholme, E. A. (1994) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1994.tb00982.x · Cited by 24 · see citing works
- Authors
- M�ller, N., Butler, P. C., Antsiferov, M. A., & Alberti, K. G. M. M.
- Affiliations
- Royal Victoria Infirmary (GB)
- ORCID
- Butler, P. C.
- Venue
- Diabetologia
- Published
- 1989-02
- Volume
- 32
- Issue
- 2
- Pages
- 105-110
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2061334119
- Semantic Scholar
- 866f4e78c32944a9587534abfda03a40e1b28cff
- Cited by
- 192
- References
- 34
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 4
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- growth hormone, insulin sensitivity, insulin resistance, forearm glucose uptake, hepatic glucose production, glucose infusion rate, glucose disposal rate, lipid intermediates, lipolysis, glucose metabolism, liver, muscle, adipose tissue
- MeSH terms
- Adult, Blood Glucose, C-Peptide, Forearm, Humans, Insulin, Male, Reference Values, Regional Blood Flow, Growth Hormone, Glucose Clamp Technique
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