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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.
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“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
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Glucocorticoids and insulin resistance: old hormones, new targets
ANDREWS, R. C., & WALKER, B. R. (1999) · Clinical Science · doi:10.1042/cs0960513 · Cited by 731
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
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
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
Andrews, R. C., Rooyackers, O., & Walker, B. R. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-021194 · Cited by 264
Metadata
- 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 › Endocrinology, Diabetes and Metabolism › 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
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