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Aldosterone decreases glucose-stimulated insulin secretion in vivo in mice and in murine islets
Open accessAbstract
Aims/hypothesisAldosterone 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.MethodsWe 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.ResultsFasting 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/interpretationWe 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.
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“We recently demonstrated that aldosterone directly impairs insulin secretion in isolated murine pancreatic islets”
From Primary aldosteronism decreases insulin secretion and increases insulin clearance in humans (2020) · cites this paper as [6]
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“genetic aldosterone deficiency markedly increases insulin secretion in mice (6, 7)”
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“aldosterone deficiency in mice increases insulin secretion in vivo without altering insulin sensitivity (6).”
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“Aldosterone impairs insulin secretion in isolated rodent islets and insulinoma cell lines”
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Zhou, S., Liu, J., Li, Z., Yang, M., Sha, R., Yan, R., Wang, X., & Cao, Y. (2024) · Hypertension Research · doi:10.1038/s41440-024-01648-0 · Cited by 4
Eight weeks of mineralocorticoid blockade does not improve insulin sensitivity in type 2 diabetes
Finsen, S. H., Hansen, M. R., Hoffmann‐Petersen, J., Højgaard, H. F., & Mortensen, S. P. (2021) · Physiological Reports · doi:10.14814/phy2.14971 · Cited by 3
Impaired Glucose Tolerance in Primary Aldosteronism
Kotchen, T. A. (2020) · Hypertension · doi:10.1161/hypertensionaha.120.14765 · Cited by 4
Adimara, A., Prahasanti, K., Prahasanti, K., Airlangga, M. P., & Airlangga, M. P. (2021) · Jurnal Ilmiah Kedokteran Wijaya Kusuma · doi:10.30742/jikw.v10i2.1453 · Cited by 3
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Protective effects of ketogenic diet on aldosterone-induced atherosclerosis in ApoE−/− mice
Armani, A., Marzolla, V., Mammi, C., Vitiello, L., Bellucci, E., Feraco, A., Gorini, S., & Caprio, M. (2025) · Journal of Endocrinological Investigation · doi:10.1007/s40618-025-02740-z · Cited by 2
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Metadata
- Authors
- Luther, J. M., Luo, P., Kreger, M. T., Brissova, M., Dai, C., Whitfield, T. T., Kim, H. S., Wasserman, D. H., Powers, A. C., & Brown, N. J.
- Affiliations
- Vanderbilt University Medical Center (US)
- University of Tennessee Health Science Center (US)
- University of North Carolina at Chapel Hill (US)
- National Institutes of Health (US)
- VA Tennessee Valley Healthcare System (US)
- Corresponding author
- Luther, J. M.
- Venue
- Diabetologia
- Published
- 2011-04-26
- Volume
- 54
- Issue
- 8
- Pages
- 2152-2163
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC3216479
- OpenAlex
- W1986937962
- Semantic Scholar
- a0c1e95c299c0afa3836d90ecaf36d72f7b3fc26
- Cited by
- 109
- References
- 52
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 9 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 4 · 2013: 10 · 2012: 11
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX000666)
- Juvenile Diabetes Research Foundation International
- Vanderbilt University (DK59637, DK20593)
- National Institutes of Health (DK-59637, DK 20593, DK66636)
- Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center (DK-20593)
- National Heart, Lung, and Blood Institute (R01HL060906, R01HL067308, HL060906, HL07738, HL067308)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK68854, K23DK081662, R01DK068764, DK089572, U01DK089572, DK69603, DK66636, DK59637, R21DK066636, R21DK068854, DK072473, DK 20593, U24DK059637, DK081662, R01DK069603, R33DK066636, U01DK072473, P30DK020593)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- aldosterone, glucose-stimulated insulin secretion, aldosterone synthase deficiency, CYP11B2, mineralocorticoid receptor, reactive oxygen species, tempol, pancreatic beta cells, insulin sensitivity, impaired glucose tolerance, obesity, diabetes mellitus, sodium intake, renin-angiotensin system, islets
- MeSH terms
- Insulin Secretion, Aldosterone, Animals, Blood Glucose, Cell Line, Glucose, Insulin, Islets of Langerhans, Male, Mice, Inbred C57BL, Cytochrome P-450 CYP11B2, Insulin-Secreting Cells, Mice, In Vitro Techniques
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