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Diabetologia. 2011 Aug;54(8):2152-63. doi: 10.1007/s00125-011-2158-9. Epub 2011 Apr 26.

Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets.

Author information

1
Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, 2200 Pierce Ave, 560 RRB, Nashville, TN 37232-6602, USA. James.Luther@Vanderbilt.edu

Abstract

AIMS/HYPOTHESIS:

Aldosterone concentrations increase in obesity and predict the onset of diabetes. We investigated the effects of aldosterone on glucose homeostasis and insulin secretion in vivo and in vitro.

METHODS:

We assessed insulin sensitivity and insulin secretion in aldosterone synthase-deficient (As [also known as Cyp11b2](-/-)) and wild-type mice using euglycaemic-hyperinsulinaemic and hyperglycaemic clamps, respectively. We also conducted studies during high sodium intake to normalise renin activity and potassium concentration in As (-/-) mice. We subsequently assessed the effect of aldosterone on insulin secretion in vitro in the presence or absence of mineralocorticoid receptor antagonists in isolated C57BL/6J islets and in the MIN6 beta cell line.

RESULTS:

Fasting glucose concentrations were reduced in As (-/-) mice compared with wild-type. During hyperglycaemic clamps, insulin and C-peptide concentrations increased to a greater extent in As (-/-) than in wild-type mice. This was not attributable to differences in potassium or angiotensin II, as glucose-stimulated insulin secretion was enhanced in As (-/-) mice even during high sodium intake. There was no difference in insulin sensitivity between As (-/-) and wild-type mice in euglycaemic-hyperinsulinaemic clamp studies. In islet and MIN6 beta cell studies, aldosterone inhibited glucose- and isobutylmethylxanthine-stimulated insulin secretion, an effect that was not blocked by mineralocorticoid receptor antagonism, but was prevented by the superoxide dismutase mimetic tempol.

CONCLUSIONS/INTERPRETATION:

We demonstrated that aldosterone deficiency or excess modulates insulin secretion in vivo and in vitro via reactive oxygen species and in a manner that is independent of mineralocorticoid receptors. These findings provide insight into the mechanism of glucose intolerance in conditions of relative aldosterone excess.

PMID:
21519965
PMCID:
PMC3216479
DOI:
10.1007/s00125-011-2158-9
[Indexed for MEDLINE]
Free PMC Article
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