Dataset Information

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

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.

SUBMITTER: Luther JM

PROVIDER: S-EPMC3216479 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Luther J M JM Luo P P Kreger M T MT Brissova M M Dai C C Whitfield T T TT Kim H S HS Wasserman D H DH Powers A C AC Brown N J NJ

Diabetologia 20110426 8

<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 21519965

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Dataset Information

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

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

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

Similar Datasets

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