The effect of cortisol on glucose/glucose-6-phosphate cycle activity and insulin action.
Abstract
Increased glucose/glucose-6-phosphate (G/G6P) substrate cycle activity may be an early marker of disordered hepatic glucose metabolism. To investigate the effects of glucocorticoids on G/G6P cycle activity and insulin resistance, we studied eight normal subjects using the euglycemic glucose clamp technique with high pressure liquid chromatography-purified [2(3)H]- and [6-3H]glucose tracers at insulin infusion rates of 0.4 and 2.0 mU/kg.min after 24-h cortisol (2 micrograms/kg.min) and saline infusions. Endogenous glucose production ([6-3H]glucose) was greater after cortisol than saline in the postabsorptive state (13.3 +/- 0.5 vs. 12.2 +/- 0.5 mumol/kg.min; P < 0.05) and during 0.4-mU insulin infusion (10.5 +/- 0.7 vs. 5.0 +/- 0.8 mumol/kg.min; P < 0.005). During 2.0-mU insulin infusion, endogenous glucose production was suppressed similarly (5.1 +/- 0.4 vs. 4.1 +/- 0.5 mumol/kg.min), but glucose disappearance was less after cortisol than saline (38.7 +/- 3.5 vs. 64.6 +/- 4.3 mumol/kg.min; P < 0.001). G/G6P cycle activity after cortisol and saline was similar in the postabsorptive state and during 0.4 mU insulin. During 2.0 mU insulin, cycle activity was greater after cortisol than saline (3.6 +/- 0.9 vs. 0.8 +/- 0.5 mumol/kg.min; P < 0.005). In conclusion, cortisol induces hepatic insulin resistance without significantly changing G/G6P cycle activity. At high glucose turnover rates, G/G6P cycle activity is increased by cortisol; however, reduced glucose disappearance is the main cause of impaired insulin action.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
The mechanism(s) responsible for cortisol-induced insulin resistance are poorly understood.
“However, the mechanism(s) responsible for cortisolinduced insulin resistance are poorly understood (28,41).”
From Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects (2004) · cites this paper as [41]
Excess cortisol induces hepatic and extrahepatic insulin resistance and alters insulin action.
“Previous studies have demonstrated that excess cortisol induces hepatic and extrahepatic insulin resistance (3,18,20,28,41,42,48).”
From Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects (2004) · cites this paper as [41]
Hydrocortisone was infused at a rate known to induce hepatic and extrahepatic insulin resistance.
“Hydrocortisone was infused at a rate known to induce hepatic and extrahepatic insulin resistance (41).”
From Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects (2004) · cites this paper as [41]
Administration of glucocorticoids to bolster late afternoon and early evening cortisol levels induces insulin resistance through post-receptor mechanisms.
“Administration of glucocorticoids to bolster cortisol levels in the late afternoon and early evening also induces insulin resistance [69, 73, 74] through post-receptor mechanisms [90–92].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [90]
Cites
Still being checked.
Cited by
Sorted by citations
Glucocorticoids and insulin resistance: old hormones, new targets
ANDREWS, R. C., & WALKER, B. R. (1999) · Clinical Science · doi:10.1042/cs0960513 · Cited by 731 · see citing works
Contributions of gluconeogenesis to glucose production in the fasted state
Landau, B. R., Wahren, J., Chandramouli, V, Schumann, W. C., Ekberg, K., & Kalhan, S. C. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118803 · Cited by 487 · see citing works
Van Raalte, D. H., Ouwens, D. M., & Diamant, M. (2009) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2008.02067.x · Cited by 439 · see citing works
Walker, B. R., Connacher, A. A., Lindsay, R. M., Webb, D. J., & Edwards, C. R. W. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.11.7593419 · Cited by 277 · see citing works
Andrews, R. C., Rooyackers, O., & Walker, B. R. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021194 · Cited by 266 · see citing works
Rafacho, A., Ortsäter, H., Nadal, A., & Quesada, I. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0373 · Cited by 216 · see citing works
The effect of altitude hypoxia on glucose homeostasis in men
Larsen, J. J., Hansen, J. M., Olsen, N. V., Galbo, H., & Dela, F. (1997) · The Journal of Physiology · doi:10.1111/j.1469-7793.1997.241bf.x · Cited by 205 · see citing works
Pathophysiology of Diabetes Mellitus in Cushing’s Syndrome
Pivonello, R., De Leo, M., Vitale, P., Cozzolino, A., Simeoli, C., De Martino, M. C., Lombardi, G., & Colao, A. (2010) · Neuroendocrinology · doi:10.1159/000314319 · Cited by 190 · see citing works
Whorwood, C. B., Donovan, S. J., Flanagan, D., Phillips, D. I. W., & Byrne, C. D. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1066 · Cited by 184 · see citing works
Hew, F. L., Koschmann, M., Christopher, M., Rantzau, C., Vaag, A. A., Ward, G. M., Beck‐Nielsen, H., & ALFORD, F. P. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.2.8636267 · Cited by 168 · see citing works
Colao, A., Block, C. E. M. D., Gaztambide, M. S., Kumar, S., Seufert, J., & Casanueva, F. F. (2013) · Pituitary · doi:10.1007/s11102-013-0483-3 · Cited by 150 · see citing works
Sleep and circadian regulation of cortisol: A short review
O'Byrne, N. A., Yuen, F., Butt, W. Z., & Liu, P. Y. (2021) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2021.03.011 · Cited by 145 · see citing works
‘Endocrine NAFLD’ a hormonocentric perspective of nonalcoholic fatty liver disease pathogenesis
Lonardo, A., Carani, C., Carulli, N., & Loria, P. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.03.005 · Cited by 144 · see citing works
Watts, L. M., Manchem, V. P., Leedom, T. A., Rivard, A. L., McKay, R. A., Bao, D., Neroladakis, T., Monia, B. P., Bodenmiller, D. M., Cao, J. X. C., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1846 · Cited by 136 · see citing works
Acute Effects of Ghrelin Administration on Glucose and Lipid Metabolism
Vestergaard, E. T., Djurhuus, C., Gjedsted, J., Nielsen, S., Møller, N., Holst, J. J., Jørgensen, J. O. L., & Schmitz, O. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2018 · Cited by 92 · see citing works
Post-Liver Transplantation Diabetes Mellitus: A Review of Relevance and Approach to Treatment
Peláez-Jaramillo, M. J., Cárdenas-Mojica, A. A., Gaete, P. V., & Mendivil, C. O. (2018) · Diabetes Therapy · doi:10.1007/s13300-018-0374-8 · Cited by 89 · see citing works
Reynolds, R. M., Walker, B. R., Syddall, H. E., Whorwood, C. B., Wood, P. J., & Phillips, D. I. W. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.3.7300 · Cited by 89 · see citing works
Sleep, testosterone and cortisol balance, and ageing men
Liu, P. Y., & Reddy, R. T. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-022-09755-4 · Cited by 80 · see citing works
Troglitazone Antagonizes Metabolic Effects of Glucocorticoids in Humans
Willi, S. M., Kennedy, A., Wallace, P., Ganaway, E., Rogers, N. L., & Garvey, W. T. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2895 · Cited by 77 · see citing works
Dzyakanchuk, A. A., Balázs, Z., Nashev, L. G., Amrein, K. E., & Odermatt, A. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.08.009 · Cited by 62 · see citing works
Insulin resistance induced by hydrocortisone is increased in patients with abdominal obesity
Darmon, P., Dadoun, F., Boullu-Ciocca, S., Grino, M., Alessi, M.-C., & Dutour, A. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00654.2005 · Cited by 59 · see citing works
Hypersomatotropism, Acromegaly, and Hyperadrenocorticism and Feline Diabetes Mellitus
Niessen, S., Church, D. B., & Forcada, Y. (2013) · Veterinary Clinics of North America Small Animal Practice · doi:10.1016/j.cvsm.2012.12.004 · Cited by 57 · see citing works
Nielsen, M. F., Caumo, A., Chandramouli, V., Schumann, W. C., Cobelli, C., Landau, B. R., Vilstrup, H., Rizza, R. A., & Schmitz, O. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00566.2002 · Cited by 53 · see citing works
Zinker, B. A., Mika, A. K., Nguyen, P., Wilcox, D. M., Öhman, L., von Geldern, T. W., Opgenorth, T. J., & Jacobson, P. B. (2007) · Metabolism · doi:10.1016/j.metabol.2006.10.021 · Cited by 48 · see citing works
Clore, J. N., Harris, P. A., Li, J., Azzam, A., Gill, R. S., Zuelzer, W. A., Rizzo, W. B., & Blackard, W. G. (2000) · Metabolism · doi:10.1016/s0026-0495(00)91455-0 · Cited by 48 · see citing works
Hypertension and other morbidities with Cushing’s syndrome associated with corticosteroids: a review
Peppa, Μ., Boutati, E. I., Krania, M., & Raptis, S. (2011) · Integrated Blood Pressure Control · doi:10.2147/ibpc.s9486 · Cited by 40 · see citing works
Substrate oxidation is altered in women during exercise upon acute altitude exposure
Beidleman, B. A., Rock, P. B., Muza, S. R., Fulco, C. S., GIBSON, L. L., Kamimori, G. H., & Cymerman, A. (2002) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-200203000-00008 · Cited by 38 · see citing works
Glucose metabolism in Cushing's syndrome
Sharma, A. R., & Vella, A. V. (2020) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000537 · Cited by 37 · see citing works
Glucocorticoid effect on insulin sensitivity: A time frame
Žarković, M., Beleslin, B., Ćirić, J., Penezić, Z., Stojković, M., Trbojević, B., Drezgić, M., & Savić, S. (2008) · Journal of Endocrinological Investigation · doi:10.1007/bf03345596 · Cited by 36 · see citing works
A gene expression signature for insulin resistance
Konstantopoulos, N., Foletta, V. C., Segal, D., Shields, K. A., Sanigorski, A. J., Windmill, K., Swinton, C., Connor, T., Wanyonyi, S. S., Dyer, T. D., et al. (2010) · Physiological Genomics · doi:10.1152/physiolgenomics.00115.2010 · Cited by 32 · see citing works
Selective Glucocorticoid Receptor (GR-II) Antagonist Reduces Body Weight Gain in Mice
Asagami, T., Belanoff, J. K., Azuma, J., Blasey, C. M., Clark, R. D., & Tsao, P. S. (2011) · Journal of Nutrition and Metabolism · doi:10.1155/2011/235389 · Cited by 31 · see citing works
Gottschalk, J., Einspanier, A., Ungemach, F. R., & Abraham, G. (2010) · Research in Veterinary Science · doi:10.1016/j.rvsc.2010.06.026 · Cited by 29 · see citing works
Abraham, G., Allersmeier, M., Schusser, G. F., & Ungemach, F. R. (2010) · The Veterinary Journal · doi:10.1016/j.tvjl.2010.05.033 · Cited by 29 · see citing works
Glucocorticoids and Insulin Sensitivity: Dissociation of Insulin’s Metabolic and Vascular Actions
Perry, C. G., Spiers, A., Cleland, S. J., Lowe, G. D. O., Petrie, J. R., & Connell, J. M. C. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021605 · Cited by 29 · see citing works
McConnell, E. M., Bell, P. M., Ennis, C., Hadden, D. R., McCance, D. R., Sheridan, B., & Atkinson, A. B. (2002) · Clinical Endocrinology · doi:10.1046/j.0300-0664.2001.01447.x · Cited by 28 · see citing works
Self-citationLiu, P. Y., Lawrence-Sidebottom, D., Piotrowska, K., Zhang, W., Iranmanesh, A., Auchus, R. J., Veldhuis, J. D., & Van Dongen, H. P. A. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab375 · Cited by 28 · see citing works
Effects of low-dose and high-dose glucagon and glucose production and gluconeogenesis in humans
Chhibbere, V. L., Soriano, C., & Tayek, J. A. (2000) · Metabolism · doi:10.1016/s0026-0495(00)90638-3 · Cited by 28 · see citing works
Stress and Glucose metabolism: A Review
Yajurvedi, H. N. (2018) · Imaging Journal of Clinical and Medical Sciences · doi:10.17352/2455-8702.000037 · Cited by 27 · see citing works
Cortisol, testosterone, and insulin action during intense swimming training in humans
Tyndall, G. L., Kobe, R. W., & Houmard, J. A. (1996) · European Journal of Applied Physiology · doi:10.1007/bf00262810 · Cited by 26 · see citing works
Short‐term metabolic effects of prednisone administration in healthy subjects
Kauh, E. A., Mixson, L. A., Shankar, S. S., McCarthy, J., Maridakis, V., Morrow, L., Heinemann, L., Ruddy, M., Herman, G. A., Kelley, D. E., et al. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01432.x · Cited by 25 · see citing works
Khadembashiri, M. M., Mohseni, S., Harandi, H., Sani, M. P., Khadembashiri, M. A., Atlasi, R., SeyedAlinaghi, S., Mohajeri‐Tehrani, M. R., & Larijani, B. A. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1374711 · Cited by 23 · see citing works
Costa, M. M., Violato, N. M., Taboga, S. R., Góes, R. M., & Bosqueiro, J. R. (2012) · International Journal of Experimental Pathology · doi:10.1111/j.1365-2613.2012.00817.x · Cited by 23 · see citing works
Spanakis, E. K., Shah, N. G., Malhotra, K., Kemmerer, T., Yeh, H., & Golden, S. H. (2014) · Hospital Practice · doi:10.3810/hp.2014.04.1100 · Cited by 22 · see citing works
Birjmohun, R. S., Bisoendial, R. J., van Leuven, S. I., Ackermans, M. T., Zwinderman, A. H., Kastelein, J. J. P., Stroes, E. S. G., & Sauerwein, H. P. (2007) · Metabolism · doi:10.1016/j.metabol.2007.06.026 · Cited by 19 · see citing works
Reduced Insulin Sensitivity as a Marker for Acute Mountain Sickness?
Spliethoff, K., Meier, D., Herter‐Aeberli, I., Gassmann, M., Langhans, W., Maggiorini, M., Lutz, T. A., & Goetze, O. (2013) · High Altitude Medicine & Biology · doi:10.1089/ham.2012.1128 · Cited by 17 · see citing works
Meng, Z., Yu, Y., Zhang, Y., Yang, X., Lv, X., Guan, F., Hatch, G. M., Zhang, M., & Chen, L. (2020) · International Journal of Biological Sciences · doi:10.7150/ijbs.39508 · Cited by 17 · see citing works
Delarue, J., Allain, G., Guillerm, S., Cruciani‐Guglielmacci, C., Magnan, C., Moineau, M., & Guen, V. L. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500469 · Cited by 14 · see citing works
Gordon, B. A., Taylor, C. J., Church, J. E., & Cousins, S. D. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18010287 · Cited by 11 · see citing works
McConnell, E. M., Atkinson, A. B., Ennis, C. N., Hadden, D. R., McCance, D. R., Sheridan, B., & Bell, P. M. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.11.8044 · Cited by 9 · see citing works
Self-citationZhou, S., Huang, J., Zhang, H., Song, X., Jiang, Y., Xu, Z. T., & Shen, X. (2025) · Journal of Dairy Science · doi:10.3168/jds.2024-25829 · Cited by 8 · see citing works
Zhou, L., Ran, X.-R., Hong, F., Li, G., & Zhu, J. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00751 · Cited by 8 · see citing works
Neely, R. D. G., HARPER, R., Rooney, D. P., Ennis, C. N., Bell, P. M., & Trimble, E. R. (1995) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.1995.tb01728.x · Cited by 5 · see citing works
Self-citationSarjan, H. N., & Yajurvedi, H. N. (2018) · International Journal of Pharmacy and Pharmaceutical Sciences · doi:10.22159/ijpps.2018v10i10.28717 · Cited by 4 · see citing works
Cushing’s glucocorticoid syndrome in the practice of a rheumatologist (A review of literature)
Satybaldyev, A. M. (2013) · Modern Rheumatology Journal · doi:10.14412/1996-7012-2013-2443 · Cited by 3 · see citing works
Jopek, K., Tyczewska, M., Szyszka, M., Blatkiewicz, M., Jopek, M., Malendowicz, L. K., & Ruciński, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713412 · Cited by 1 · see citing works
Leydig Cells, Testosterone, Sleep, and Andrological Health
Liu, P. Y. (2025) · Springer eBooks · doi:10.1007/978-3-031-96376-6_35 · Cited by 1 · see citing works
Impact of Drugs on Diabetes Risk and Glycemic Control
Frontoni, S., & Picconi, F. (2019) · Endocrinology · doi:10.1007/978-3-319-27316-7_19-2 · Cited by 1 · see citing works
Impact of Drugs on Diabetes Risk and Glycemic Control
Frontoni, S., & Picconi, F. (2018) · Endocrinology · doi:10.1007/978-3-319-44433-8_19 · Cited by 1 · see citing works
Wittmann, G. (2008) · Hungarian Medical Journal · doi:10.1556/hmj.2.2008.28343 · Cited by 1 · see citing works
Einfluss von normobarer Hypoxie auf die Fettutilisation bei einer Laufausdauerbelastung
Isbary, G. J. (2006) · Cited by 1 · see citing works
Asudani, D., & Calles-Escandón, J. (2007) · Journal of Hospital Medicine · doi:10.1002/jhm.249 · Cited by 1 · see citing works
Corticosteroid hormone action in the cardiovascular system
Hammer, F. (2011) · UPT. Syiah Kuala University Library (Syiah Kuala University)
11beta-hydroxysteroid dehydrogenase type 1 as a pharmacological target in metabolic disease
Hult, M. (2004) · Figshare
Insulin action on large artery stiffness in normal and insulin resistant subjects
Westerbacka, J. (2001) · Työväentutkimus Vuosikirja
Title of dissertation: HIGH SUCROSE, FRUCTOSE, AND GLUCOSE DIETS AND GLUCOCORTICOID DYSREGULATION IN
London, E., & Castonguay, T. W. (2009)
Гл юкокортикоидный синдром Кушинга в практике ревматолога (обзор литературы)
Satybaldyev, A. M., & Nasonova, V. A. (2013)
Guelfi, K. J. (2006) · UWA Profiles and Research Repository (UWA)
Exploring the Function of G6PC2 in Pancreatic Islet Beta Cells
Boortz, K. A. (2016)
Social stress, obesity and glucose tolerance: a psychobiological investigation
Sanghez, V. (2012) · DSpaceUnipr (University of Parma)
Impact of Drugs on Diabetes Risk and Glycemic Control
Frontoni, S., & Picconi, F. (2018) · Endocrinology · doi:10.1007/978-3-319-27316-7_19-1
Impact of Drugs on Diabetes Risk and Glycemic Control
Frontoni, S., & Picconi, F. (2020) · Endocrinology · doi:10.1007/978-3-030-36694-0_19
Physiological effects of steroids
Honour, J. W. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-818124-9.00015-2
Ferrière, A., & Tabarin, A. (2025) · Médecine des Maladies Métaboliques · doi:10.1016/j.mmm.2025.07.002
Regulation of intra-adipose cortisol concentrations in vivo in humans
Hughes, K. A. (2011) · ERA
- Authors
- Rooney, D. P., Neely, R. D., Cullen, C., Ennis, C. N., Sheridan, B., Atkinson, A. B., Trimble, E. R., & Bell, P. M.
- Affiliations
- Royal Victoria Hospital (GB)
- ORCID
- Neely, R D
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1993-11
- Volume
- 77
- Issue
- 5
- Pages
- 1180-1183
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1990313681
- Cited by
- 76
- References
- 0
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 5 · 2016: 3 · 2014: 2 · 2013: 5 · 2012: 2
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- cortisol, glucocorticoids, hepatic insulin resistance, hepatic glucose metabolism, endogenous glucose production, glucose disappearance, insulin action
- MeSH terms
- Absorption, Adult, Blood Glucose, Female, Glucose, Glucosephosphates, Humans, Hydrocortisone, Insulin, Male, Glucose Clamp Technique, Glucose-6-Phosphate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
