Cited by 419Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes and associated disorders

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Direct glucocorticoid inhibition of insulin secretion. An in vitro study of dexamethasone effects in mouse islets.

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Lambillotte, C, Gilon, P, Henquin, J C·1997·Journal of Clinical Investigation

DOI 10.1172/jci119175PMC PMC507814

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Abstract

The direct effects of glucocorticoids on pancreatic beta cell function were studied with normal mouse islets. Dexamethasone inhibited insulin secretion from cultured islets in a concentration-dependent manner: maximum of approximately 75% at 250 nM and IC50 at approximately 20 nM dexamethasone. This inhibition was of slow onset (0, 20, and 40% after 1, 2, and 3 h) and only slowly reversible. It was prevented by a blocker of nuclear glucocorticoid receptors, by pertussis toxin, by a phorbol ester, and by dibutyryl cAMP, but was unaffected by an increase in the fuel content of the culture medium. Dexamethasone treatment did not affect islet cAMP levels but slightly reduced inositol phosphate formation. After 18 h of culture with or without 1 microM dexamethasone, the islets were perifused and stimulated by a rise in the glucose concentration from 3 to 15 mM. Both phases of insulin secretion were similarly decreased in dexamethasone-treated islets as compared with control islets. This inhibition could not be ascribed to a lowering of insulin stores (higher in dexamethasone-treated islets), to an alteration of glucose metabolism (glucose oxidation and NAD(P)H changes were unaffected), or to a lesser rise of cytoplasmic Ca2+ in beta cells (only the frequency of the oscillations was modified). Dexamethasone also inhibited insulin secretion induced by arginine, tolbutamide, or high K+. In this case also the inhibition was observed despite a normal rise of cytoplasmic Ca2+. In conclusion, dexamethasone inhibits insulin secretion through a genomic action in beta cells that leads to a decrease in the efficacy of cytoplasmic Ca2+ on the exocytotic process.

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Authors: Lambillotte, C., Gilon, P., & Henquin, J. C.
Affiliations: UCLouvain (BE)
ORCID: Gilon, P
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1997-02-01
Volume: 99
Issue: 3
Pages: 414-423
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119175
PMC: PMC507814
OpenAlex: W2047680032
Cited by: 419
References: 59
Citations by year: 2026: 3 · 2025: 13 · 2024: 9 · 2023: 14 · 2022: 9 · 2021: 18 · 2020: 13 · 2019: 17 · 2018: 9 · 2017: 10 · 2016: 17 · 2015: 27 · 2014: 26 · 2013: 23 · 2012: 30
FWCI: 4.99
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
Funders: Fédération Wallonie-Bruxelles
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords: dexamethasone, glucocorticoids, insulin secretion, pancreatic beta cells, pancreatic islets, glucocorticoid receptor, pertussis toxin, phorbol ester, cyclic AMP, inositol phosphates, intracellular calcium, exocytosis, glucose-stimulated insulin secretion, L-arginine, tolbutamide, high potassium stimulation, glucose metabolism
MeSH terms: Insulin Secretion, Cyclic AMP, Animals, Arginine, B-Lymphocytes, Calcium, Cells, Cultured, Dexamethasone, Bucladesine, Dose-Response Relationship, Drug, Glucocorticoids, Glucose, Inositol Phosphates, Insulin, Islets of Langerhans, Male, Mice, Inbred Strains, NADP, Oxidation-Reduction, Virulence Factors, Bordetella, Phorbol Esters, Potassium, Receptors, Glucocorticoid, Tolbutamide, Pertussis Toxin, Mice

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Direct glucocorticoid inhibition of insulin secretion. An in vitro study of dexamethasone effects in mouse islets.

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