On the Role of Glucocorticoid in Glucose-Induced Insulin Secretion

Kawai, Atsuo; Kuzuya, Nobusada

doi:10.1055/s-0028-1093528

Cited by 33 publications

(20 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Overall, the plasma insulin concentrations correlated positively to cortisol. Although glucocorticoids are generally thought to reduce glucose-stimulated insulin secretion (1,5,33), a chronic decrease in glucocorticoids also inhibits insulin secretion (15). The increase in cortisol in the present study may not be sufficient to inhibit insulin production, and the association with cortisol in the present study may be indirect, reflecting pancreatic compensation for chronic glucose intolerance.…”

Section: Discussioncontrasting

confidence: 48%

Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy

Keller‐Wood

Feng

Wood

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Keller-Wood M, Feng X, Wood CE, Richards E, Anthony RV, Dahl GE, Tao S. Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy. Am J Physiol Regul Integr Comp Physiol 307: R405-R413, 2014. First published June 11, 2014 doi:10.1152/ajpregu.00530.2013.-In normal pregnancy, cortisol increases; however, further pathological increases in cortisol are associated with maternal and fetal morbidities. These experiments were designed to test the hypothesis that increased maternal cortisol would increase maternal glucose concentrations, suppress fetal growth, and impair neonatal glucose homeostasis. Ewes were infused with cortisol (1 mg·kg Ϫ1 ·day Ϫ1 ) from day 115 of gestation to term; maternal glucose, insulin, ovine placental lactogen, estrone, progesterone, nonesterified free fatty acids (NEFA), ␤-hydroxybutyrate (BHB), and electrolytes were measured. Infusion of cortisol increased maternal glucose concentration and slowed the glucose disappearance after injection of glucose; maternal infusion of cortisol also increased the incidence of fetal death at or near parturition. The design of the study was altered to terminate the study prior to delivery, and post hoc analysis of the data was performed to test the hypothesis that maternal metabolic factors predict the fetal outcome. In cortisol-infused ewes that had stillborn lambs, plasma insulin was increased relative to control ewes or cortisol-infused ewes with live lambs. Maternal cortisol infusion did not alter maternal food intake or plasma NEFA, BHB, estrone, progesterone or placental lactogen concentrations, and it did not alter fetal body weight, ponderal index, or fetal organ weights. Our study suggests that the adverse effect of elevated maternal cortisol on pregnancy outcome may be related to the effects of cortisol on maternal glucose homeostasis, and that chronic maternal stress or adrenal hypersecretion of cortisol may create fetal pathophysiology paralleling some aspects of maternal gestational diabetes. glucose; insulin; cortisol; pregnancy MATERNAL CORTISOL IS INCREASED in normal human pregnancy and is thought to contribute to the increase in maternal glucose concentration, as well as supporting increases in maternal plasma volume and cardiac output. In studies done in our laboratory, we have found that increasing maternal cortisol beyond the normal doubling in ovine pregnancy led to increased uterine blood flow and maternal and fetal glucose and lactate concentrations, whereas decreasing maternal cortisol to concentrations similar to those of nonpregnant ewes resulted in reduced uterine blood flow as gestation advanced (12, 13). Either increased or decreased maternal cortisol concentrations slowed the rate of fetal growth between 115 and 130 days of gestation. In women with Cushing's disease or Cushing's syndrome in pregnancy, there is also an increased incidence of small-for-gestational-age babies, as well as an increased risk of adverse pregnancy outcomes (26, 34). Maternal glucocorticoid treatme...

show abstract

Section: Discussioncontrasting

confidence: 48%

Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy

Keller‐Wood

Feng

Wood

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…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].…”

mentioning

confidence: 99%

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

et al. 2008

View full text Add to dashboard Cite

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.

show abstract

“…Complex results have also been yielded by studies in which rats or mice were treated with glucocorticoids and insulin secretion was subsequently measured in vitro. Augmented (12)(13)(14)(15), unchanged (16,17), and decreased (14,18,19) insulin secretion has been reported. These differences are not easily explained and appear to depend on the dose of glucocorticoid, the length of administration, the propensity of the animal strain to develop diabetes, and the stimulus used in vitro.…”

Section: Introductionmentioning

confidence: 99%

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

Lambillotte¹,

Gilon²,

Henquin³

1997

J. Clin. Invest.

368

308

View full text Add to dashboard Cite

The direct effects of glucocorticoids on pancreatic ␤ cell function were studied with normal mouse islets. Dexamethasone inhibited insulin secretion from cultured islets in a concentration-dependent manner: maximum of ‫ف‬ 75% at 250 nM and IC 50 at ‫ف‬ 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 M 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 Ca 2 ϩ in ␤ cells (only the frequency of the oscillations was modified). Dexamethasone also inhibited insulin secretion induced by arginine, tolbutamide, or high K ϩ . In this case also the inhibition was observed despite a normal rise of cytoplasmic Ca 2 ϩ . In conclusion, dexamethasone inhibits insulin secretion through a genomic action in ␤ cells that leads to a decrease in the efficacy of cytoplasmic Ca 2 ϩ on the exocytotic process. ( J. Clin. Invest. 1997. 99:414-423.)

show abstract

On the Role of Glucocorticoid in Glucose-Induced Insulin Secretion

Cited by 33 publications

References 2 publications

Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy

Elevated maternal cortisol leads to relative maternal hyperglycemia and increased stillbirth in ovine pregnancy

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

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

Contact Info

Product

Resources

About