Vasopressin and hydration play a major role in the development of glucose intolerance and hepatic steatosis in obese rats
Open accessAbstract
Aims/hypothesis High plasma copeptin, a marker of vasopressin (VP) secretion, has been shown to be associated with the metabolic syndrome and development of type 2 diabetes in humans. The present study was designed to determine the long-term influence of plasma VP concentration in a rodent model prone to metabolic dysfunction.Methods Obese Zucker rats and their lean counterparts were submitted for 4 weeks to one of three protocols inducing different levels of VP. Circulating VP was either reduced by increasing the daily water intake (low-VP), or increased by a chronic i.p. infusion of VP (high-VP). The control rats had normal VP levels that depended on their own regulation of water intake and VP secretion.Results Compared with controls with normal VP, lean rats with high-VP had a higher fasting glycaemia after 4 weeks. In obese rats, high-VP promoted hyperinsulinaemia, glucose intolerance, assessed by glucose and insulin tolerance tests, and an impaired response to a pyruvate challenge. Conversely, treatment with a selective arginine vasopressin receptor 1A (V1aR) antagonist reduced glucose intolerance. Low-VP obese rats had unchanged glucose tolerance but exhibited a drastic decrease in liver steatosis compared with control obese rats, associated with low hepatic triacylglycerol and cholesterol content, and reduced expression of hepatic lipogenic genes. These effects were independent of changes in body adiposity, and plasma sodium and osmolality did not differ among groups.Conclusion/interpretation These findings show a causal relationship between the VP-hydration axis and the metabolic risk. Therapeutic perspectives include diet recommendations regarding hydration, but also potential pharmacological interventions targeting the VP V1aR.
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- Findingown data
In obese high-vasopressin rats, hepatic Avpr1a mRNA abundance was 50% higher than in norm-vasopressin rats (1.52±0.15 vs 1.00±0.15, p<0.01).
“Obese high-VP rats exhibited a 50% higher Avpr1a mRNA abundance than the norm-VP rats (1.52±0.15vs 1.00±0.15,p<0.01)”
Quote in the paperNot a substantial claim - Findingown data
At week 4, lean high-vasopressin rats had fourfold higher insulinaemia than norm-vasopressin rats (146±26 vs 34±9 pmol/l, p<0.05).
“paralleled by fourfold higher values of insulinaemia in the high-VP group (146±26 vs 34± 9 pmol/l, p<0.05).”
Quote in the paperSubstantial claim - Findingown data
At week 4, lean high-vasopressin rats had fasting glycaemia 1.5 mmol/l higher than norm-vasopressin rats.
“At week 4, the glycaemic difference between high-and norm-VP groups amounted to 1.5 mmol/l”
Quote in the paperSubstantial claim - Findingown data
In lean rats, low vasopressin slightly decreased fasting glycaemia compared with norm vasopressin.
“Low-VP level slightly decreased fasting glycaemia”
Quote in the paperNot a substantial claim - Findingown data
In obese rats, low vasopressin/high hydration markedly decreased hepatic cholesterol content compared with norm vasopressin.
“Low-VP/high hydration markedly decreased triacylglycerol and cholesterol content compared with norm-VP-treated animals (Fig. 5b, c)”
Quote in the paperSubstantial claim
- Findingown data
In obese rats, high vasopressin increased glucose excursion after pyruvate challenge, with peak glycaemia twofold greater than in other groups.
“The glucose excursion in the next 2 h was markedly increased by high-VP treatment, peaking with a twofold greater glycaemia than in the other groups (Fig. 2f).”
Quote in the paperSubstantial claim - Findingown data
During insulin tolerance tests in obese rats, plasma insulin levels 15 min after insulin injection were significantly higher in high vasopressin than in other groups (4,138±130, 3,194±4,047, 2,419±426 pmol/l, p<0.03).
“During ITT, plasma insulin levels reached significantly higher values in high-VP rats than in other rats 15 min after insulin injection (4,138 ± 130, 3,194 ± 4,047 and 2,419 ± 426 pmol/l in high-VP, norm-VP, and low-VP groups, respectively, p < 0.03) because of differences in basal values (Fig. 3b).”
Quote in the paperNot a substantial claim - Findingown data
In obese rats, mild necroinflammation was observed in liver.
“Mild necroinflammation was observed.”
Quote in the paperNot a substantial claim - Findingown data
In obese rats during glucose tolerance tests, V1a receptor antagonist decreased the amplitude of glycaemic response by 35% compared with control.
“During the GTT, the amplitude of glycaemic response was significantly decreased by 35% in the V1aR-antagonist group compared with the control group”
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In obese rats, neither portal nor perisinusoidal fibrosis was detected in the different groups.
“Neither portal nor perisinusoidal fibrosis was detected in the different groups.”
Quote in the paperNot a substantial claim - Findingown data
In obese rats, at 2 weeks, an intraperitoneal glucose load induced a twofold higher glycaemia response in high vasopressin than in other groups.
“At this time point, an i.p. glucose load induced a twofold higher level of glycaemia and insulinaemia response in the high-VP group compared with the other groups (Fig. 2d, e and Table 3).”
Quote in the paperSubstantial claim - Findingown data
In obese rats during glucose tolerance tests, V1a receptor antagonist did not significantly change insulin response compared with control.
“whereas the amplitude of insulin response was not significantly different between the groups (Fig. 4a, b).”
Quote in the paperNot a substantial claim - Findingown data
In obese rats, glucagon concentration changes following hypoglycaemia were similar in all groups.
“However, the main candidate for such counter-regulation, i.e. glucagon, showed similar changes in concentration following hypoglycaemia in all groups (Fig. 3c).”
Quote in the paperSubstantial claim - Findingown data
In obese Zucker rats, chronic vasopressin infusion increased fasting insulinaemia (674±107 before, 1,449±112 after 2 weeks, 1,217±65 pmol/l after 4 weeks, p<0.001).
“However, chronic VP infusion induced a significant increase in fasting insulinaemia (674±107, 1,449±112, 1,217±65 pmol/l before, and after 2 or 4 weeks of treatment, respectively, p<0.001) (Fig. 2b).”
Quote in the paperSubstantial claim - Findingown data
In obese rats, high vasopressin produced a 50% higher insulin resistance index than the other groups after 2 weeks.
“Thus, the IR index was already 50% higher in the high-VP group than in the two other groups after 2 weeks of treatment (Fig. 2c).”
Quote in the paperSubstantial claim - Findingown data
In low vasopressin rats, water intake and urine volume were markedly higher than in norm vasopressin.
“As expected, water intake and urine volume were markedly higher in low-VP than in the norm-VP group.”
Quote in the paperNot a substantial claim - Findingown data
In lean Zucker rats, chronic high vasopressin produced a progressive rise in fasting glycaemia.
“Chronic high VP level resulted in a progressive rise in fasting glycaemia in lean rats (Fig. 1a).”
- Also stated in: § Abstract · plain
“Compared with controls with normal VP, lean rats with high-VP had a higher fasting glycaemia after 4 weeks.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
In obese rats, low vasopressin was associated with increased hepatic glycogen content.
“Low-VP was also associated with an increase in hepatic glycogen content (Fig. 5d).”
Quote in the paperNot a substantial claim - Findingown data
In lean rats, high vasopressin impaired glucose tolerance as shown by glucose tolerance tests.
“Glucose tolerance was significantly impaired in the high-VP group as demonstrated by the GTT results (Fig. 1b).”
Quote in the paperSubstantial claim - Findingown data
In obese rats, despite differences in insulinaemia, the initial fall in glycaemia during insulin tolerance tests was similar between groups.
“Despite these differences in insulinaemia, the initial fall in glycaemia was similar between groups (Fig. 3a)”
Quote in the paperNot a substantial claim - Findingown data
In lean and obese rats, vasopressin infusion increased daily urinary vasopressin excretion 10- to 25-fold in high vasopressin compared with norm vasopressin.
“The infusion of VP resulted in a 10-to 25-fold increase in daily urinary VP excretion in high-VP rats of both genotypes compared with norm-VP rats.”
Quote in the paperSubstantial claim - Findingown data
In obese rats, at 2 weeks, an intraperitoneal glucose load induced a twofold higher insulinaemia response in high vasopressin than in other groups.
“At this time point, an i.p. glucose load induced a twofold higher level of glycaemia and insulinaemia response in the high-VP group compared with the other groups (Fig. 2d, e and Table 3).”
Quote in the paperSubstantial claim - Findingown data
In lean rats, high vasopressin produced a fourfold higher insulin resistance index than norm vasopressin.
“Consequently, the IR index was fourfold higher in the high-VP than in the norm-VP groups of rats.”
Quote in the paperSubstantial claim - Findingown data
In obese rats, treatments did not change the proportion of body fat after 4 weeks (48±1, 46±1, 44±1% for low vasopressin, norm vasopressin, and high vasopressin).
“Treatments did not change the proportion of body fat in obese rats after 4 weeks of treatment (48±1, 46±1, 44 ±1% relative to body weight in low-VP, norm-VP and high-VP groups, respectively).”
Quote in the paperNot a substantial claim - Findingown data
In obese rats after 4 weeks, fasting insulinaemia was significantly lower in V1a receptor antagonist than control (643±180 vs 1,526±163 pmol/l, p<0.001).
“but fasting insulinaemia was significantly lower in the V1aR-antagonist group than in the control group (643 ± 180 vs 1,526 ± 163 pmol/l, p<0.001).”
Quote in the paperSubstantial claim - Findingown data
In obese rats, high vasopressin did not change mRNA abundance of genes for gluconeogenesis, glycogenolysis, or hepatic glucose transporters.
“Treatments did not change the mRNA abundance of genes coding for enzymes involved in gluconeogenesis and glycogenolysis or the expression of hepatic glucose transporters (see ESM Table 1).”
Quote in the paperNot a substantial claim - Findingown data
In obese rats, high vasopressin and norm vasopressin had similar degrees and types of liver steatosis, characterised by mediovesicles and macrovacuoles mainly in centro- and medio-lobular areas.
“Histological analysis of liver showed that high-VP and norm-VP obese rats had similar degrees and types of steatosis, characterised by mediovesicles and macrovacuoles mainly localised in the centro-and medio-lobular areas.”
Quote in the paperSubstantial claim - Findingown data
In obese rats after 4 weeks, fasting blood glycaemia did not differ significantly between V1a receptor antagonist and control groups (5.34±0.21 vs 5.16±0.16 mmol/l).
“After 4 weeks of treatment, fasting blood glycaemia levels were not significantly different between the groups (5.34 ± 0.21 vs 5.16 ± 0.16 mmol/l in the V1aRantagonist and control groups, respectively)”
Quote in the paperNot a substantial claim - Findingown data
In obese low-vasopressin rats with high hydration, almost no liver steatosis was present after 2 weeks.
“Interestingly, low-VP rats with high hydration had almost no steatosis after 2 weeks of treatment (Fig. 5a).”
- Also stated in: § Abstract · plain
“Low-VP obese rats had unchanged glucose tolerance but exhibited a drastic decrease in liver steatosis compared with control obese rats”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
In lean and obese rats, chronic increase in water intake lowered urinary vasopressin excretion in low vasopressin to about one-tenth of norm vasopressin.
“The chronic increase in water intake lowered urinary VP excretion in low-VP rats to about one-tenth that in control norm-VP rats in both obese and lean rats.”
Quote in the paperNot a substantial claim - Findingown data
In obese rats, low vasopressin decreased hepatic gene expression of FAS, SREBP-1c, and AQP-9 compared with norm vasopressin.
“as well as gene expression of proteins involved in lipogenesis, fatty acid synthase (FAS), sterol regulatory element binding protein 1c (SREBP-1c) and aquaporin 9 (AQP-9) (Fig. 5e-h).”
- Also stated in: § Abstract · plain
“reduced expression of hepatic lipogenic genes.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
In obese rats, the insulin resistance index was about half in V1a receptor antagonist compared with control (23±7 vs 49±4, p<0.01).
“Consequently, the IR index was reduced to about half in the V1aR-antagonist group compared with the non-treated control group (23±7 vs 49±4, p<0.01).”
Quote in the paperSubstantial claim - Findingown data
In obese rats, insulin intraperitoneal injection induced similar glycaemic changes in V1a receptor antagonist and control groups.
“Insulin i.p. injection induced a similar pattern of glycaemic changes in both groups (Fig. 4c).”
Quote in the paperNot a substantial claim - Findingown data
In obese rats, low vasopressin/high hydration markedly decreased hepatic triacylglycerol content compared with norm vasopressin.
“Low-VP/high hydration markedly decreased triacylglycerol and cholesterol content compared with norm-VP-treated animals (Fig. 5b, c)”
Quote in the paperSubstantial claim - Findingown data
In lean rats, low vasopressin did not change the glucose response during glucose tolerance tests compared with norm vasopressin.
“but it did not change the glucose response during GTT compared with the norm-VP group (Fig. 1a, b).”
Quote in the paperNot a substantial claim - Findingown data
High vasopressin induced a moderate but significant hyperglycaemic effect in lean rats.
“High VP induced a moderate but significant hyperglycaemic effect in lean rats.”
Quote in the paperSubstantial claim - Findingown data
In obese rats, low vasopressin did not change glucose tolerance compared with control obese rats.
“Low-VP obese rats had unchanged glucose tolerance but exhibited a drastic decrease in liver steatosis compared with control obese rats”
Quote in the paperSubstantial claim - Findingown data
The groups did not differ significantly in plasma osmolality.
“although plasma osmolality was not significantly different between the groups”
Quote in the paperNot a substantial claim - Findingown data
The study groups did not differ in their circulating apelin levels.
“the finding of similar concentrations of circulating apelin in the different groups of the present study”
Quote in the paperSubstantial claim - Findingown data
In obese rats, high vasopressin and norm vasopressin had no differences in plasma triacylglycerol, total cholesterol, or fasting blood glycaemia.
“No differences were observed in the plasma concentrations of triacylglycerol or total cholesterol or in fasting blood glycaemia (Table 2, Fig. 2a) between the differently treated groups of obese rats.”
Quote in the paperNot a substantial claim - Findingown data
Blocking V1a receptors reduces glucose intolerance in obese Zucker rats.
“V1aR antagonism attenuates glucose intolerance in obese Zucker rats.”
Quote in the paperSubstantial claim - Findingown data
Exposure to high vasopressin induces disorders in glucose metabolism as early as 2 weeks after onset in both lean and obese Zucker rats.
“Our results show that exposure to a high VP level induces disorders in glucose metabolism as early as 2 weeks after onset of the VP treatment in both lean and obese Zucker rats.”
Quote in the paperSubstantial claim - Findingown data
In obese Zucker rats, a high VP level worsens glucose intolerance.
“High VP level aggravates glucose intolerance in obese Zucker rats.”
Quote in the paperSubstantial claim - Findingown data
In obese rats, treatment with a V1aR antagonist for a chronic period reduced fasting insulin levels and the glucose tolerance test response.
“Moreover, chronic V1aR antagonist treatment decreased fasting insulinaemia and GTT response in obese rats.”
Quote in the paperSubstantial claim - Premisecitation
Water intake is inversely and independently associated with the risk of developing hyperglycaemia in a general French population cohort.
“We reported that water intake was inversely and independently associated with the risk of developing hyperglycaemia in a cohort of the general French population [19].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] Roussel R, Fezeu L, Bouby N et al (2011) Low water intake and risk for new-onset hyperglycemia. Diabetes Care 34:2551–2554 source
Not checked in the free run.
- Interpretationown data
In obese rats, high vasopressin animals had lower sensitivity to insulin, partly evidenced by the insulin resistance index.
“suggesting a lower sensitivity to insulin in high-VP animals that was partly evidenced by calculation of the IR index.”
Quote in the paperSubstantial claim - Interpretationreasoning
A high level of circulating vasopressin has adverse consequences on glucose metabolism.
“These observations suggest that a high level of circulating VP has adverse consequences on glucose metabolism, although a causal link between a sustained high level of VP and disorders of glucose homeostasis has not been established.”
Quote in the paperSubstantial claim- The authors state this as an assumption: A causal link between sustained high vasopressin and disorders of glucose homeostasis has not been established.
- Interpretationown data
In obese rats, V1a receptor blockade partially restores glucose tolerance.
“Conversely, treatment with a selective arginine vasopressin receptor 1A (V1aR) antagonist reduced glucose intolerance.”
- Also stated in: § Results · plain
“V1aR blockade partially restores glucose tolerance in obese rats”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Interpretationown data
In obese rats, low vasopressin protects liver tissue from steatosis by preventing upregulation of lipogenesis.
“Low-VP protects liver tissue from steatosis in obese rats by preventing upregulation of lipogenesis”
Quote in the paperSubstantial claim - Premisecitation
Vasopressin stimulates release of glucagon or insulin from pancreatic islets through V1b receptors, depending on extracellular glucose.
“and the release of either glucagon or insulin, depending on concomitant extracellular glucose levels, through the activation of arginine vasopressin receptor 1B (V1bR) in pancreatic islets [7][8][9].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [7] Lee B, Yang C, Chen TH, al-Azawi N, Hsu WH (1995) Effect of AVP and oxytocin on insulin release: involvement of V1b receptors. Am J Physiol 269:E1095–E1100
Not checked in the free run.
- cites [8] Yibchok-Anun S, Cheng H, Chen TH, Hsu WH (2000) Mechanisms of AVP-induced glucagon release in clonal alpha-cells in-R1-G9: involvement of Ca(2+)-dependent and -independent pathways. Br J Pharmacol 129:257–264 source
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- cites [9] Abu-Basha EA, Yibchok-Anun S, Hsu WH (2002) Glucose dependency of arginine vasopressin-induced insulin and glucagon release from the perfused rat pancreas. Metabolism 51:1184–1190 source
Not checked in the free run.
- Premisecitation
Acute vasopressin infusion in rats and healthy individuals causes a transient rise in blood glucose.
“Acute VP infusion in the rat and in healthy individuals was shown to induce a transient rise in blood glucose concentration [4][5][6].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [4] Hems DA, Whitton PD, Ma GY (1975) Metabolic actions of vasopressin, glucagon and adrenalin in the intact rat. Biochim Biophys Acta 411:155–164 source
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- cites [5] Rofe AM, Williamson DH (1983) Metabolic effects of vasopressin infusion in the starved rat. Reversal of ketonaemia. Biochem J 212:231–239 source
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- cites [6] Spruce BA, McCulloch AJ, Burd J et al (1985) The effect of vasopressin infusion on glucose metabolism in man. Clin Endocrinol (Oxf) 22:463–468 source
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- Premisecitation
Vasopressin stimulates gluconeogenesis and glycogenolysis through hepatic V1a receptors.
“Ex vivo studies showed that VP stimulates gluconeogenesis and glycogenolysis through the activation of hepatic arginine VP receptor 1A (V1aR)”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [7] Lee B, Yang C, Chen TH, al-Azawi N, Hsu WH (1995) Effect of AVP and oxytocin on insulin release: involvement of V1b receptors. Am J Physiol 269:E1095–E1100
Not checked in the free run.
- cites [8] Yibchok-Anun S, Cheng H, Chen TH, Hsu WH (2000) Mechanisms of AVP-induced glucagon release in clonal alpha-cells in-R1-G9: involvement of Ca(2+)-dependent and -independent pathways. Br J Pharmacol 129:257–264 source
Not checked in the free run.
- cites [9] Abu-Basha EA, Yibchok-Anun S, Hsu WH (2002) Glucose dependency of arginine vasopressin-induced insulin and glucagon release from the perfused rat pancreas. Metabolism 51:1184–1190 source
Not checked in the free run.
- Premisecitation
Mice with deleted V1a and/or V1b receptors exhibit metabolic disorders.
“The finding that mice with deleted V1aR and/or V1bR exhibit metabolic disorders [12][13][14][15] has prompted several epidemiological investigations in humans.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [12] Aoyagi T, Birumachi J, Hiroyama M et al (2007) Alteration of glucose homeostasis in V1a vasopressin receptor-deficient mice. Endocrinology 148:2075–2084 source
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- cites [13] Fujiwara Y, Hiroyama M, Sanbe A et al (2007) Insulin hypersensitivity in mice lacking the V1b vasopressin receptor. J Physiol 584:235–244 source
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- cites [14] Nakamura K, Aoyagi T, Hiroyama M et al (2009) Both V(1A) and V(1B) vasopressin receptors deficiency result in impaired glucose tolerance. Eur J Pharmacol 613:182–188 source
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- Interpretationown data
The different patterns in the late portion of insulin tolerance tests suggest differences in counter-regulatory responses to insulin-induced hypoglycaemia.
“These different patterns in the late portion of the ITT suggest differences in the counter-regulatory responses to insulin-induced hypoglycaemia.”
Quote in the paperNot a substantial claim - Premisecitation
A proposed mechanism for high-VP-related glucose intolerance and insulin resistance is that intracellular glucose metabolism is impaired by enhanced gluconeogenesis and/or glycogenolysis.
“One is impaired intracellular glucose metabolism due to increased gluconeogenesis and/or increased glycogenolysis as suggested by acute experiments [31,32], an effect probably related to V1aR activation [29].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [31] Hems DA, Whitton PD (1973) Stimulation by vasopressin of glycogen breakdown and gluconeogenesis in the perfused rat liver. Biochem J 136:705–709 source
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- cites [32] Wideman CH, Murphy HM (1993) Modulatory effects of vasopressin on glucose and protein metabolism during food-restriction stress. Peptides 14:259–261 source
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- cites [29] Morel A, O’Carroll AM, Brownstein MJ, Lolait SJ (1992) Molecular cloning and expression of a rat V1a arginine vasopressin receptor. Nature 356:523–526 source
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- Interpretationown data
In our model, VP's impact on liver fat accumulation and on glucose tolerance were not parallel.
“Of note, the effects of VP on hepatic lipid accumulation and glucose tolerance are dissociated in our model.”
Quote in the paperSubstantial claim - Study design and conductcitation
The bidirectional vasopressin protocol mimicked the wide interindividual variability of usual vasopressin concentration and osmotic thresholds for thirst and vasopressin secretion in humans.
“This 'bidirectional' protocol mimicked the wide interindividual variability of the usual VP concentration and osmotic thresholds for thirst and VP secretion observed in humans [30].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] Zerbe RL, Miller JZ, Robertson GL (1991) The reproducibility and heritability of individual differences in osmoregulatory function in normal human subjects. J Lab Clin Med 117:51–59
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- Interpretationown data
The effects of low vasopressin on liver steatosis and hepatic lipids were independent of changes in body adiposity.
“These effects were independent of changes in body adiposity, and plasma sodium and osmolality did not differ among groups.”
Quote in the paperSubstantial claim - Interpretationreasoning
For individuals at risk of diabetes who are inadequately hydrated, drinking somewhat more water might help prevent or delay hyperglycaemia and later diabetes, along with its kidney complications.
“Overall, these findings suggest that, in people who are at risk of diabetes and have an inappropriate hydration status, a moderate increase in water intake, a costless lifestyle change not exclusive of other recommendations, may help prevent or delay the onset of hyperglycaemia and subsequent diabetes, together with its renal complications.”
Quote in the paperSubstantial claim- Rests on an assumption: Results from obese Zucker rats can be extrapolated to humans at risk of diabetes.
- Interpretationown data
The reduced Fasn and Srebf1 mRNA in low-VP rats points to a decline in de novo fatty acid synthesis.
“The lower mRNA abundance of Fasn and Srebf1 as in the low-VP group suggests a decrease in de novo synthesis of fatty acids”
Quote in the paperSubstantial claim- Rests on an assumption: Hepatic mRNA levels of Fasn and Srebf1 reflect the rate of de novo fatty acid synthesis.
- Interpretationown data
The glucose metabolism abnormalities seen in this study are probably not mediated by glucagon.
“However, glucagon is not likely to play a role in the disturbances of glucose metabolism observed in the present study because basal plasma glucagon concentration and glucagon response during ITT were unaltered by chronic VP treatment.”
Quote in the paperNot a substantial claim- Rests on an assumption: If glucagon contributed to the observed glucose metabolism disturbances, basal plasma glucagon or the glucagon response to ITT would have been altered.
- Premisecitation
Hyperosmolality-induced shrinkage of hepatocytes has been shown to suppress the synthesis of proteins and glycogen.
“Hepatocytes shrinkage induced by hyperosmolality has been shown to inhibit protein and glycogen synthesis [34].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [34] Lang F, Busch GL, Ritter M et al (1998) Functional significance of cell volume regulatory mechanisms. Physiol Rev 78:247–306 source
Not checked in the free run.
- Interpretationreasoning
Because Srebf2 mRNA was unchanged, the lower cholesterol content in the low-VP group likely results from increased cholesterol breakdown rather than reduced synthesis.
“The unaltered mRNA expression of Srebf2, the key regulator for the cholesterol biosynthesis, suggests that the decrease in cholesterol content in the low-VP group is due to an increase in cholesterol degradation rather than a decrease in synthesis.”
Quote in the paperNot a substantial claim- Rests on an assumption: Srebf2 is the key regulator of cholesterol biosynthesis.
- Interpretationown data
The lack of difference in circulating apelin argues against an effect mediated by apelin.
“However, the finding of similar concentrations of circulating apelin in the different groups of the present study does not support an apelin-mediated effect.”
Quote in the paperSubstantial claim- Rests on an assumption: If apelin mediated the effect on steatosis, circulating apelin levels would differ between groups.
- Interpretationown data
In obese rats, high vasopressin effects on glucose metabolism were at least partly through V1a receptors.
“The present study reveals that a sustained high VP level alters glucose metabolism, increasing glycaemia in lean healthy rats, and impairing glucose tolerance in obese rats, at least partly through V1aR.”
Quote in the paperSubstantial claim - Premisecitation
VP's vasoconstrictive action, which lowers hepatic blood flow, may trigger glycogen breakdown through hypoxia.
“Vasoconstrictive effects of VP and the resulting decrease in hepatic blood flow could cause hypoxia-driven glycogenolysis [4].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4] Hems DA, Whitton PD, Ma GY (1975) Metabolic actions of vasopressin, glucagon and adrenalin in the intact rat. Biochim Biophys Acta 411:155–164 source
Not checked in the free run.
- Interpretationown data
The findings support a causal link for the epidemiological associations between high copeptin or low water intake and the occurrence of hyperglycaemia, metabolic syndrome, and type 2 diabetes.
“They clearly support a causality link in the associations observed in epidemiological studies between high copeptin level or low water intake and the prevalence and incidence of hyperglycaemia, metabolic syndrome and type 2 diabetes.”
Quote in the paperSubstantial claim- Rests on an assumption: Results from obese Zucker rats can be extrapolated to humans at risk of diabetes.
- Interpretationown data
Low vasopressin and high hydration alleviate hepatic steatosis associated with obesity in this model.
“The results of this study point also to a beneficial effect of low VP level and high hydration to alleviate the hepatic steatosis associated with obesity in this model.”
Quote in the paperSubstantial claim - Interpretationreasoning
The reduction in steatosis caused by high water intake is probably mediated by the fall in plasma VP.
“Although the effect of high water intake on the reduction in steatosis is likely due to the reduction in VP plasma level, other hormonal changes related to increased water intake could be involved.”
Quote in the paperSubstantial claim - Study design and conductnone given
In both lean and obese rat models, VP levels were changed in opposite directions over several weeks.
“The VP level was altered in two opposite directions for several weeks in two different rat models (lean and obese).”
Quote in the paperSubstantial claim - Interpretationreasoning
In low-VP rats, the drop in triacylglycerol content is probably due in part to lower fatty acid availability and reduced Aqp9 expression.
“This decrease in fatty acid availability, in addition to decreased expression of Aqp9 , the major pathway of glycerol entry in hepatocytes, is probably responsible, at least in part, for the fall in triacylglycerol content.”
Quote in the paperSubstantial claim- Rests on an assumption: Aqp9 is the main route for glycerol entry into hepatocytes.
- May combine two claims. 24
- Classified as probably not a substantial claim. 17
- The quote only partly states this claim. 2
May combine two claims.
Findingown dataIn obese low-vasopressin rats, hepatic Avpr1a mRNA tended to be 25% lower than in norm-vasopressin rats, but not significantly (0.73±0.13).
“while low-VP rats tended to show a 25% decline (0.73±0.13, non-significant).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn obese low-vasopressin rats, sustained hypoglycaemia persisted throughout insulin tolerance tests, with significantly lower glycaemia at 90 and 120 min.
“Sustained hypoglycaemia persisted in low-VP rats throughout the test, with significantly lower values of glycaemia at time points 90 and 120 min ( p < 0.01)”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn obese rats, chronic V1a receptor antagonism did not change body growth or water metabolism compared with controls.
“No difference in body growth or parameters of water metabolism was observed between the rats receiving V1aR-antagonist and control rats (see ESM Table 2).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn obese rats, glycaemia returned faster to baseline during insulin tolerance tests in high vasopressin than in norm vasopressin, resulting in slightly lower AUC values.
“Glycaemia returned faster to baseline level in high-VP rats than in norm-VP rats, resulting in slightly lower AUC values (Table 3).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataPlasma osmolality, natraemia, kaliaemia, and haematocrit did not differ significantly among the three vasopressin groups.
“There was no significant difference in plasma osmolality, natraemia, kaliaemia or haematocrit between the different groups.”
- Also stated in: § Abstract · plain
“plasma sodium and osmolality did not differ among groups.”
Quote in the paperSubstantial claim- Also stated in: § Abstract · plain
May combine two claims.
FindingcitationIn high vasopressin rats, vasopressin infusion did not change fluid intake, urine volume, or osmolality compared with norm vasopressin.
“In contrast, VP infusion did not change fluid intake, urine volume and osmolality in the high-VP group compared with the norm-VP group.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
FindingreasoningDaily osmolar excretion was comparable among low vasopressin, norm vasopressin, and high vasopressin groups.
“Daily osmolar excretion was comparable in all three groups, as expected from the equivalent food intake imposed on all rats.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn obese Zucker rats, high hydration lowers VP and reverses fatty liver.
“Low VP level induced by high hydration reverses hepatosteatosis in obese Zucker rats.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataRats excreted extra water appropriately, with no sign of plasma dilution, as indicated by unchanged plasma sodium and haematocrit.
“Rats excreted this extra water appropriately as no sign of plasma dilution appeared, as indicated by unchanged plasma sodium concentration and haematocrit.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataGlucose tolerance tests and insulin tolerance tests revealed that high vasopressin promotes glucose intolerance and accelerates recovery after insulin-induced hypoglycaemia.
“Consistent with this observation, GTT and ITT revealed that high VP promotes glucose intolerance and accelerates recovery after insulin-induced hypoglycaemia.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn fasted obese rats, high vasopressin induced a marked increase in insulinaemia compared with control, with no difference in plasma glucose.
“In fasted obese rats, high VP induced a marked increase in insulinaemia compared with the control group, with no difference in plasma glucose.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn high-VP rats, pyruvate challenge showed higher glycaemia and increased glucose production, and liver V1aR was upregulated.
“This hypothesis is supported by higher glycaemia and increased production of glucose observed during the pyruvate challenge and the upregulation of V1aR in the liver of high-VP rats.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataObese rats with low VP did not have better glucose tolerance than control obese rats, yet they showed a clear reduction in hepatic steatosis, with lower liver triacylglycerol and cholesterol.
“Low-VP rats did not display improved glucose tolerance compared with control obese rats but exhibited a marked decrease in hepatic steatosis with low hepatic content in triacylglycerol and cholesterol.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataHigh water intake increased daily urine volume markedly but not enough to induce hypo-osmotic urine.
“The high water intake increased the daily urine volume markedly, but not enough to induce the formation of hypo-osmotic urine.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataObese rats with high VP had worse glucose tolerance but their hepatic steatosis did not worsen.
“High-VP rats displayed impairment of glucose tolerance but no aggravation of hepatic steatosis.”
Quote in the paperSubstantial claimThe quote only partly states this claim.
FindingreasoningObese rats with high VP levels recovered more quickly from insulin-induced hypoglycaemia.
“The faster recovery after insulin-induced hypoglycaemia observed in the high-VP group”
Quote in the paperNot a substantial claimThe quote only partly states this claim.
FindingreasoningObese rats with low VP had reduced hepatic mRNA levels of Fasn and Srebf1.
“The lower mRNA abundance of Fasn and Srebf1 as in the low-VP group”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataLong-term VP treatment left basal plasma glucagon levels and the glucagon response to an insulin tolerance test unchanged.
“basal plasma glucagon concentration and glucagon response during ITT were unaltered by chronic VP treatment.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationVasopressin stimulates adrenocorticotropin hormone release through pituitary V1b receptors.
“Furthermore, VP stimulates adrenocorticotropin hormone release through the activation of pituitary V1bR [10,11].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [10] Gillies GE, Linton EA, Lowry PJ (1982) Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin. Nature 299:355–357 source
Not checked in the free run.
- cites [11] Serradeil-Le Gal C, Wagnon J, Simiand J et al (2002) Characterization of (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N, N-dimethyl-2-pyrrolidine carboxamide (SSR149415), a selective and orally active vasopressin V1b receptor antagonist. J Pharmacol Exp Ther 300:1122–1130 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHigh plasma copeptin predicts future diabetes mellitus independently of known risk factors.
“High plasma copeptin predicted future diabetes mellitus independently of known risk factors [18].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Enhorning S, Wang TJ, Nilsson PM et al (2010) Plasma copeptin and the risk of diabetes mellitus. Circulation 121:2102–2108 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationVasopressin contributes to albuminuria and diabetes-induced nephropathy in animal models.
“Additionally, VP was shown to contribute to albuminuria and to diabetes-induced nephropathy in animal models [20,21].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [20] Bardoux P, Bichet DG, Martin H et al (2003) Vasopressin increases urinary albumin excretion in rats and humans: involvement of V2 receptors and the renin-angiotensin system. Nephrol Dial Transplant 18:497–506 source
Not checked in the free run.
- cites [21] Bankir L, Bouby N, Ritz E (2013) Vasopressin: a novel target for the prevention and retardation of kidney disease? Nat Rev Nephrol 9:223–239 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPlasma vasopressin is increased in patients with type 1 or type 2 diabetes and in animal models of diabetes.
“Although it has been known for several decades that plasma vasopressin (VP) is increased in patients with type 1 or with type 2 diabetes mellitus [1] and in animal models of diabetes [2,3]”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [1] Zerbe RL, Vinicor F, Robertson GL (1979) Plasma vasopressin in uncontrolled diabetes mellitus. Diabetes 28:503–508 source
Not checked in the free run.
- cites [2] Brooks DP, Nutting DF, Crofton JT, Share L (1989) Vasopressin in rats with genetic and streptozocin-induced diabetes. Diabetes 38:54–57 source
Not checked in the free run.
- cites [3] Yi SS, Hwang IK, Kim YN et al (2008) Enhanced expressions of arginine vasopressin (Avp) in the hypothalamic paraventricular and supraoptic nuclei of type 2 diabetic rats. Neurochem Res 33:833–841 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationEpidemiological studies in humans are consistent with vasopressin contributing to albuminuria and diabetes-induced nephropathy.
“Epidemiological studies in humans are consistent with these findings [21][22][23].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [21] Bankir L, Bouby N, Ritz E (2013) Vasopressin: a novel target for the prevention and retardation of kidney disease? Nat Rev Nephrol 9:223–239 source
Not checked in the free run.
- cites [22] Meijer E, Bakker SJ, Halbesma N, de Jong PE, Struck J, Gansevoort RT (2010) Copeptin, a surrogate marker of vasopressin, is associated with albuminuria in a large population cohort. Kidney Int 77:29–36 source
Not checked in the free run.
- cites [23] Velho G, Bouby N, Hadjadj S et al (2013) Plasma copeptin and renal outcomes in patients with type 2 diabetes and albuminuria. Diabetes Care 36:3639–3645 source
Not checked in the free run.
May combine two claims.
PremisecitationIn humans, high plasma copeptin is associated with insulin resistance, metabolic syndrome and obesity.
“Plasma copeptin, a stable surrogate marker for VP derived from the same preprohormone [16], has been shown to be associated with insulin resistance, metabolic syndrome and obesity [17].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Saleem U, Khaleghi M, Morgenthaler NG et al (2009) Plasma carboxy-terminal provasopressin (copeptin): a novel marker of insulin resistance and metabolic syndrome. J Clin Endocrinol Metab 94:2558–2564 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationGlucagon is an important regulator of glucose balance and contributes to the development of high blood glucose in diabetes.
“Besides insulin, glucagon is a major hormone in glucose homeostasis and plays a role in the pathogenesis of hyperglycaemia in diabetes (as reviewed by Cryer PE [35]).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [35] Cryer PE (2012) Minireview: glucagon in the pathogenesis of hypoglycemia and hyperglycemia in diabetes. Endocrinology 153:1039–1048 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn a large population sample, a frequent variant of the human AVPR1A gene is linked to disturbed glucose homeostasis.
“This experimental observation is in line with the association reported between a common genetic variant in the human AVPR1A gene and impaired glucose homeostasis in a large population-based sample [33].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [33] Enhorning S, Leosdottir M, Wallstrom P et al (2009) Relation between human vasopressin 1a gene variance, fat intake, and diabetes. Am J Clin Nutr 89:400–406 source
Not checked in the free run.
May combine two claims.
PremisecitationAssimacopoulos-Jeannet and colleagues found that VP stimulated fat synthesis in isolated hepatocytes, but this effect disappeared when lactate in the medium was raised, which itself increased baseline lipogenesis.
“Assimacopoulos-Jeannet et al [48] showed that VP increased lipogenesis in isolated hepatocytes, but when concentration of lactate in the medium was increased, basal lipogenesis was increased and the stimulatory effect of VP was lost.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [48] Assimacopoulos-Jeannet F, Denton RM, Jeanrenaud B (1981) Stimulation of hepatic lipogenesis and acetyl-coenzyme A carboxylase by vasopressin. Biochem J 198:485–490 source
Not checked in the free run.
May combine two claims.
Interpretationown dataThese interventions showed that the VP/hydration system significantly affects basal blood glucose, glucose tolerance, and liver steatosis.
“The results of these experimental interventions revealed a significant influence of the VP/ hydration system not only on basal glycaemia and glucose tolerance but also on liver steatosis.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSome mouse models of obesity and non-insulin-dependent diabetes have also shown a dissociation between fatty liver and glucose tolerance.
“A similar dissociation was already reported in some murine models of obesity and non-insulin dependent diabetes mellitus [44,45].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [44] Wendel AA, Li LO, Li Y, Cline GW, Shulman GI, Coleman RA (2010) Glycerol-3-phosphate acyltransferase 1 deficiency in ob/ob mice diminishes hepatic steatosis but does not protect against insulin resistance or obesity. Diabetes 59:1321–1329 source
Not checked in the free run.
- cites [45] Moon YA, Liang G, Xie X et al (2012) The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell Metab 15:240–246 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn hepatocytes, interactions between the V1a receptor and the glucagon receptor and their signalling pathways have been reported.
“Crosstalk between V1aR and glucagon receptor and their signalling pathways has been described also in hepatocytes [37,38].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [37] Morgan NG, Shipp CC, Exton JH (1983) Studies on the mechanism of inhibition of hepatic cAMP accumulation by vasopressin. FEBS Lett 163:277–281 source
Not checked in the free run.
- cites [38] Chabardes D, Imbert-Teboul M, Elalouf JM (1999) Functional properties of Ca2+-inhibitable type 5 and type 6 adenylyl cyclases and role of Ca2+ increase in the inhibition of intracellular cAMP content. Cell Signal 11:651–663 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationApelin has been implicated in disorders of glucose metabolism and in liver fibrosis.
“Apelin has been shown to be involved in glucose metabolism disorders and in hepatic fibrosis [52,53].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [52] Knauf C, Drougard A, Fournel A, Duparc T, Valet P (2013) Hypothalamic actions of apelin on energy metabolism: new insight on glucose homeostasis and metabolic disorders. Horm Metab Res 45:928–934 source
Not checked in the free run.
- cites [53] Principe A, Melgar-Lesmes P, Fernandez-Varo G et al (2008) The hepatic apelin system: a new therapeutic target for liver disease. Hepatology 48:1193–1201 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAt high insulin levels, the kidney is the main site of insulin degradation, more so than the liver.
“it has been reported that renal insulin degradation is predominant compared with liver at high insulin concentrations [40]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [40] Koschorreck M, Gilles ED (2008) Mathematical modeling and analysis of insulin clearance in vivo. BMC Syst Biol 2:43 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationVP increases glomerular filtration rate.
“VP increases glomerular filtration rate [41,42]”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [41] Bouby N, Ahloulay M, Nsegbe E, Dechaux M, Schmitt F, Bankir L (1996) Vasopressin increases glomerular filtration rate in conscious rats through its antidiuretic action. J Am Soc Nephrol 7:842–851 source
Not checked in the free run.
- cites [42] Bardoux P, Martin H, Ahloulay M et al (1999) Vasopressin contributes to hyperfiltration, albuminuria, and renal hypertrophy in diabetes mellitus: study in vasopressin-deficient Brattleboro rats. Proc Natl Acad Sci U S A 96:10397–10402 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn obesity, fatty liver has frequently been linked to hepatic insulin resistance.
“Steatosis has often been associated with hepatic IR in the context of obesity [43].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [43] den Boer M, Voshol PJ, Kuipers F, Havekes LM, Romijn JA (2004) Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal models. Arterioscler Thromb Vasc Biol 24:644–649 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationResearch on VP and fat synthesis has yielded conflicting findings.
“Previous studies on VP and lipogenesis have reported contradictory results [4,[46][47][48].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [4,[46][47][48]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationVP may raise glucagon release either by activating V1b receptors in pancreatic islets or indirectly by promoting adrenaline secretion from the adrenal medulla.
“Glucagon secretion could be increased by VP through activation of V1bR in pancreatic islets [7][8][9], or indirectly by stimulating adrenaline (epinephrine) secretion by chromaffin cells of the adrenal medulla [36].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [7][8][9]
Not checked in the free run.
- cites [36] Guillon G, Grazzini E, Andrez M et al (1998) Vasopressin: a potent autocrine/paracrine regulator of mammal adrenal functions. Endocr Res 24:703–710 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationApelin and VP are released in response to opposite shifts in plasma osmolality and have opposing actions in the acute central and renal control of water balance.
“Apelin and VP are secreted in response to opposite changes in plasma osmolality and exert opposite effects in acute regulation of water balance both centrally and at the level of the kidney [49][50][51].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [49][50][51]
Not checked in the free run.
May combine two claims.
Interpretationown dataSustained high vasopressin alters glucose metabolism, increasing glycaemia in lean healthy rats and impairing glucose tolerance in obese rats.
“The present study reveals that a sustained high VP level alters glucose metabolism, increasing glycaemia in lean healthy rats, and impairing glucose tolerance in obese rats, at least partly through V1aR.”
Quote in the paperSubstantial claim
The authors state this as an assumption.
A causal link between sustained high vasopressin and disorders of glucose homeostasis has not been established.
“although a causal link between a sustained high level of VP and disorders of glucose homeostasis has not been established.”
The authors state this as an assumption.
No previous study had investigated the chronic influence of vasopressin on liver metabolism in vivo.
“no previous study to our knowledge investigated the chronic influence of VP on liver metabolism in vivo.”
The authors state this as an assumption.
This is the first study assessing the role of chronic alterations in vasopressin level on glucose metabolism.
“To our knowledge, this is the first study assessing the role of chronic alterations in VP level on glucose metabolism.”
The paper relies on this without support.
The secretion of vasopressin and copeptin strongly depends on the level of hydration.
“The secretion of VP and copeptin strongly depends on the level of hydration.”
The paper relies on this without support.
SR49059 is a selective V1a receptor antagonist.
“obese rats treated with the selective non-peptide V1aR antagonist SR49059”
The paper relies on this without support.
No earlier study has examined the chronic metabolic effects of VP in living animals.
“In conclusion, our study is the first addressing the chronic metabolic actions of VP in vivo.”
The paper relies on this without support.
Results from obese Zucker rats can be extrapolated to humans at risk of diabetes.
“Overall, these findings suggest that, in people who are at risk of diabetes and have an inappropriate hydration status, a moderate increase in water intake, a costless lifestyle change not exclusive of other recommendations, may help prevent or delay the onset of hyperglycaemia and subsequent diabetes, together with its renal complications.”
The paper relies on this without support.
If glucagon contributed to the observed glucose metabolism disturbances, basal plasma glucagon or the glucagon response to ITT would have been altered.
“However, glucagon is not likely to play a role in the disturbances of glucose metabolism observed in the present study because basal plasma glucagon concentration and glucagon response during ITT were unaltered by chronic VP treatment.”
The paper relies on this without support.
If apelin mediated the effect on steatosis, circulating apelin levels would differ between groups.
“However, the finding of similar concentrations of circulating apelin in the different groups of the present study does not support an apelin-mediated effect.”
The paper relies on this without support.
Srebf2 is the key regulator of cholesterol biosynthesis.
“The unaltered mRNA expression of Srebf2, the key regulator for the cholesterol biosynthesis, suggests that the decrease in cholesterol content in the low-VP group is due to an increase in cholesterol degradation rather than a decrease in synthesis.”
The paper relies on this without support.
Aqp9 is the main route for glycerol entry into hepatocytes.
“decreased expression of Aqp9 , the major pathway of glycerol entry in hepatocytes”
The paper relies on this without support.
Hepatic mRNA levels of Fasn and Srebf1 reflect the rate of de novo fatty acid synthesis.
“The lower mRNA abundance of Fasn and Srebf1 as in the low-VP group suggests a decrease in de novo synthesis of fatty acids”
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.
ITT AUCs are higher, not lower, in the high-VP group
MinorThe text says faster recovery in high-VP rats produced lower AUCs than in norm-VP rats. Table 3 lists higher high-VP glycaemia AUCs at both week 2 (172 versus 146) and week 4 (130 versus 113).
“Glycaemia returned faster to baseline level in high-VP rats than in norm-VP rats, resulting in slightly lower AUC values (Table 3).”
“| Glycaemia (mmol/l.2 h) | 316±15 *** 146±15 172±19 † † † | | | | Insulinaemia (nmol/l.2 h) | 168±27 * 254±36 314±12** | | | | Glucagonaemia (pmol/l.2 h) 1,274±57 1,304±39 1,260±61 | | | | | ITT week 4 | | | | | Glycaemia (mmol/l.2 h) | 134±25 | 113±24 130±18 | |”
The citation lists haven’t been fetched yet
References 57 · Cited by 86
- Authors
- Taveau, C., Chollet, C., Waeckel, L., Desposito, D., Bichet, D. G., Arthus, M.-F., Magnan, C., Philippe, E., Paradis, V., Foufelle, F., Hainault, I., Enhorning, S., Velho, G., Roussel, R., Bankir, L., Melander, O., & Bouby, N.
- Affiliations
- Inserm (FR)
- Hôpital du Sacré-Cœur de Montréal (CA)
- Centre National de la Recherche Scientifique (FR)
- Lund University (SE)
- Corresponding author
- Bouby, Nadine
- ORCID
- Venue
- Diabetologia
- Published
- 2015-01-27
- Volume
- 58
- Issue
- 5
- Pages
- 1081-1090
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W1976141421
- Semantic Scholar
- eee9ef6347c719738d5e4a124de25c148c9a476f
- Cited by
- 86
- References
- 57
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 1 · 2022: 4 · 2021: 9 · 2020: 10 · 2019: 11 · 2018: 11 · 2017: 13 · 2016: 9 · 2015: 1
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Hjärt-Lungfonden
- Novo Nordisk
- Vetenskapsrådet
- Université Paris Descartes
- Université Pierre et Marie Curie
- Novo Nordisk Fonden (NNF14OC0009819, NNF13OC0005339)
- FP7 Ideas: European Research Council (282255)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- vasopressin, hydration, impaired glucose tolerance, hepatic steatosis, obesity, copeptin, AVPR1A, hyperinsulinemia, hepatic lipogenesis, metabolic syndrome, type 2 diabetes, water intake, Zucker rats
- MeSH terms
- Animals, Blood Glucose, Drinking, Fatty Liver, Glucose Tolerance Test, Indoles, Male, Obesity, Pyrrolidines, Rats, Zucker, Vasopressins, Glucose Intolerance, Antidiuretic Hormone Receptor Antagonists
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