Glucocorticoids and insulin resistance: old hormones, new targets

ANDREWS, Robert C.; WALKER, Brian R.

doi:10.1042/cs0960513

Cited by 731Diabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic DiseasesAdrenal Hormones and Disorders

Glucocorticoids and insulin resistance: old hormones, new targets

ANDREWS, Robert C., WALKER, Brian R.·1999·Clinical Science

DOI 10.1042/cs0960513

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Abstract

Insulin resistance has been proposed as a mediator of the association between risk factors for cardiovascular disease in the population. The clinical syndrome of glucocorticoid excess (Cushing's syndrome) is associated with glucose intolerance, obesity and hypertension. By opposing the actions of insulin, glucocorticoids could contribute to insulin resistance and its association with other cardiovascular risk factors. In this review, we describe briefly the known mechanisms of insulin resistance and highlight the potential mechanisms for the effect of glucocorticoids. We then discuss factors which modulate the influence of glucocorticoids on insulin sensitivity; this highlights a novel therapeutic strategy to manipulate glucocorticoid action which may prove to be a useful tool in treating subjects with insulin resistance. Finally, we describe evidence from human studies that glucocorticoids make an important contribution to the pathophysiology of insulin resistance in the population.

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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 [3]
Key driving mechanisms of secondary diabetes under hypercortisolism include stimulation of gluconeogenesis, development of insulin resistance, and impairment of pancreatic insulin secretion.
“some key driving mechanisms have been identified such as the stimulation of gluconeogenesis and development of insulin resistance, together with the impairment of pancreatic insulin secretion ( 23, 24 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [24]
Endogenous glucose release from the liver is active primarily during fasting but diminished following glucose intake from meals or OGTTs.
“we also consider endogenous glucose release from the liver ( 24 ), a process that we modelled as active primarily during fasting but diminished following glucose intake from meals or OGTTs.”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [24]

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Authors: ANDREWS, R. C., & WALKER, B. R.
Affiliations: Western General Hospital (GB)
ORCID: ANDREWS, Robert C.
WALKER, Brian R.
Venue: Clinical Science
Publisher: Portland Press Ltd.
Published: 1999-04-16
Volume: 96
Issue: 5
Pages: 513-523
ISSN: 0143-5221 (ISSN-L)
1470-8736
DOI: 10.1042/cs0960513
OpenAlex: W2042443117
Cited by: 731
References: 7
Citations by year: 2026: 9 · 2025: 14 · 2024: 28 · 2023: 28 · 2022: 18 · 2021: 13 · 2020: 23 · 2019: 29 · 2018: 26 · 2017: 27 · 2016: 32 · 2015: 31 · 2014: 40 · 2013: 37 · 2012: 49
FWCI: 9.68
Type: journal article
Language: en
Open access: closed
Locations: Clinical Science (publishedVersion)
PubMed (publishedVersion)
Explore Bristol Research (submittedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: glucocorticoids, insulin resistance, Cushing's syndrome, impaired glucose tolerance, obesity, hypertension, cardiovascular risk factors, insulin sensitivity, therapeutic target
MeSH terms: Cardiovascular Diseases, Glucose, Humans, Hydrocortisone, Hydroxysteroid Dehydrogenases, Insulin Resistance, Liver, Models, Biological, Obesity, Risk Factors, 11-beta-Hydroxysteroid Dehydrogenases

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Glucocorticoids and insulin resistance: old hormones, new targets

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