Effect of adrenal steroids on insulin release from cultured rat islets of Langerhans

Pierluissi, J.; Navas, F.; Ashcroft, S. J. H.

doi:10.1007/bf00456122

Cited by 67 publications

(54 citation statements)

References 10 publications

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“…The effects of glucocorticoid on insulin secretion are dependent upon the dose and duration of administration [8]. While most studies report inhibition of insulin secretion by glucocorticoids [5,[9][10][11], long-term culture in hydrocortisone [12] and dexamethasone-treatment of islets from adrenalectomised rats [13] increase insulin release. However, transgenic mice overexpressing GR (also known as NR3C1) specifically in the beta cell have impaired glucose tolerance due to decreased insulin release, suggesting a direct inhibitory action of glucocorticoid upon the beta cell [14].…”

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confidence: 99%

11β-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets

et al. 2008

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Aims/hypothesis Exposure to excess glucocorticoid is associated with pancreatic beta cell damage and decreased glucose-stimulated insulin secretion (GSIS). Inactive glucocorticoids (cortisone, 11-dehydrocorticosterone) are converted to active cortisol and corticosterone by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which requires NADPH as cofactor, which is generated by hexose-6-phosphate dehydrogenase (H6PDH). We investigated the localisation and activity of 11β-HSD1 within pancreatic islets, and determined its functional role in the regulation of insulin and glucagon secretion. Methods mRNA expression of 11β-HSD1 (also known as HSD11B1), glucocorticoid receptor and H6PDH (also known as H6PD) in human pancreas and murine islets was examined by real-time PCR. 11β-HSD1 protein levels were examined by immunohistochemistry and immunofluorescence. 11β-HSD1 activity was assessed in intact tissue and isolated islets of wild-type (WT) and both 11β-Hsd1-and H6pdh-null mice. Glucagon secretion and insulin secretion were analysed by RIA and ELISA respectively in isolated murine islets incubated with dexamethasone. Results 11β-HSD1 co-localised with glucagon in the periphery of murine and human islets, but not with insulin or somatostatin. Dexamethasone, 11-dehydrocorticosterone and corticosterone induced a dose-dependent decrease in GSIS and glucagon secretion following low glucose stimulation. Reduction of 11β-HSD1 activity with specific inhibitors or in experiments carried out in H6pdh-null mice reversed the effects of 11-dehydrocorticosterone, but had no effect following treatment with corticosterone. Conclusions/interpretation Local regeneration of glucocorticoid via 11β-HSD1 within alpha cells regulates glucagon secretion and in addition may act in a paracrine manner to limit insulin secretion from beta cells.

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confidence: 99%

11β-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets

et al. 2008

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“…The reduced GSIS under 6.3 µM for 2 h culture was also seen with 7.5, 10, 12.5, 15, 20 and 30 mM glucose. These responses were re-established after 4 h. Pred and Hydr also induced decreased GSIS and none of these drugs elicit a decrease in islet insulin content (Pierluissi et al, 1986) …”

Section: Hours To Days Gc Effectsmentioning

confidence: 87%

“…Details regarding GC compounds used, concentrations, duration of treatment, and main effects on -cell function are described in Table 4. The GC-induced reduction in GSIS could not be attributed to decreases in insulin content since it was unchanged or augmented (Pierluissi et al, 1986;Gremlich et al, 1997;Lambillotte et al, 1997;Zawalich et al, 2006), although reduction was also observed under certain conditions (Jeong et al, 2001). It has been shown that presence of DEX in islet or -cell culture medium induces reduction (Gremlich et al, 1997) or no change (Shao et al, 2004) in GLUT 2 protein content, decrease in -cell GK (Shao et al, 2004) and pyruvate dehydrogenase (PDH) (Arumugam et al, 2010) activities, and increased pyruvate dehydrogenase kinase (PDK)-2 mRNA content (Arumugam et al, 2010).…”

Section: Hours To Days Gc Effectsmentioning

confidence: 95%

Functional and Molecular Aspects of Glucocorticoids in the Endocrine Pancreas and Glucose Homeostasis

Rafacho¹,

Boschero²,

Ortsäter³

2012

State of the Art of Therapeutic Endocrinology

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“…However, such investigations have also produced conflicting results, probably because of various study designs, GC preparations used, dosages, and time of exposure, as well as different characteristics of the studied cells. The majority of studies indicate an inhibitory GC effect on insulin secretion in vitro [50][51][52][53][54][55][56]. The effect is dosedependent and abolished by addition of GR antagonist RU486 to the cell culture [47,[56][57][58][59][60].…”

Section: Inhibitory Glucocorticoid Effect On Insulin Secretion In Vitromentioning

confidence: 99%

Glikokortykosteroidy a czynność komórek beta

Fichna

2017

Endokrynologia Polska

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Glucocorticoids (GCs) play a pivotal role in carbohydrate metabolism. They counteract insulin by decreasing peripheral glucose uptake and stimulating hepatic gluconeogenesis, although they are best known for inducing insulin resistance (IR). Moreover, GCs may attenuate the incretin effect. Nevertheless, their direct impact on beta cells is not fully defined. This review aims to present the current understanding of this subject. Humans exposed to GC excess display IR, impaired glucose tolerance, and eventually develop diabetes. Although their insulin levels are elevated, they present lower insulin output in response to glucose than obese individuals. Rodent models demonstrate that GC-induced IR is accompanied by compensatory beta-cell hyperplasia. GC excess with high-fat diet leads to fasting hyperglycaemia and suppressed glucose-stimulated insulin secretion (GSIS) despite increased beta cell mass. The majority of in vitro studies confirm an inhibitory GC effect on insulin secretion. The mechanism remains ambiguous but might involve its direct influence upon expression of molecules essential for glucose sensing and metabolism, enhanced glucose cycling, down-regulated insulin gene transcription, hampered insulin exocytosis, amplified alpha-adrenergic signalling, and/or increased beta-cell apoptosis. There are also reports that suggest increased GSIS after beta cell exposure to GCs in vitro. Transgenic mice with enhanced corticosterone regeneration within their beta cells present augmented secretory capacity of their islets. To summarise, GCs exert a significant role in carbohydrate balance through various mechanisms, including direct impact on beta cell function. Observed discrepancies may arise from differences in study design. A thorough understanding of GC action will provide important clinical clues for disorders of glucose homeostasis. (Endokrynol Pol 2017; 68 (5): 568-573)

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Effect of adrenal steroids on insulin release from cultured rat islets of Langerhans

Cited by 67 publications

References 10 publications

11β-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets

11β-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets

Functional and Molecular Aspects of Glucocorticoids in the Endocrine Pancreas and Glucose Homeostasis

Glikokortykosteroidy a czynność komórek beta

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