FEBS Open Bio. 2014 Jan 18;4:141-6. doi: 10.1016/j.fob.2014.01.005. eCollection 2014.
DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet.
FEBS open bio
Katherine Veras, Felipe Natali Almeida, Renato Tadeu Nachbar, Daniel Simões de Jesus, João Paulo Camporez, Angelo Rafael Carpinelli, Julia H Goedecke, Carla Roberta de Oliveira Carvalho
Affiliations
Affiliations
- Department of Physiology and Biophysics, ICB 1, USP, São Paulo, SP, Brazil.
- South African Medical Research Council and Department of Human Biology, University of Cape Town, Cape Town, South Africa.
PMID: 24490138
PMCID: PMC3907747 DOI: 10.1016/j.fob.2014.01.005
Abstract
Dehydroepiandrosterone (DHEA) and the dehydroepiandrosterone sulfate (DHEA-S) are steroids produced mainly by the adrenal cortex. There is evidence from both human and animal models suggesting beneficial effects of these steroids for obesity, diabetes mellitus, hypertension, and osteoporosis, conditions associated with the post-menopausal period. Accordingly, we hypothesized that DHEA supplementation in ovariectomized (OVX) female rats fed a high-fat diet would maintain glucose-induced insulin secretion (GSIS) and pancreatic islet function. OVX resulted in a 30% enlargement of the pancreatic islets area compared to the control rats, which was accompanied by a 50% reduction in the phosphorylation of AKT protein in the pancreatic islets. However, a short-term high-fat diet induced insulin resistance, accompanied by impaired GSIS in isolated pancreatic islets. These effects were reversed by DHEA treatment, with improved insulin sensitivity to levels similar to the control group, and with increased serine phosphorylation of the AKT protein. These data confirm the protective effect of DHEA on the endocrine pancreas in a situation of diet-induced overweight and low estrogen concentrations, a phenotype similar to that of the post-menopausal period.
Keywords: DHEA, dehydroepiandrosterone; DHEA-S, dehydroepiandrosterone sulfate; GSIS, glucose-induced insulin secretion; GTT, glucose tolerance test; HFD, high-fat diet; High fat diet; Insulin secretion; Insulin sensitivity; Kitt, glucose disappearance rate; Menopause; OHL, ovariectomized rats fed HFD; OHLD, ovariectomized rats fed a HFD and treated with DHEA; OVX, ovariectomized rats; PI, propidium iodide; PI3K, phosphatidylinositol-3-kinase; PI3K-PDK1-Akt, PI3K-3-phosphoinositide dependent kinase-Akt; Pancreatic islets; SDS–PAGE, sodium dodecyl sulfate poly-acrylamide electrophoresis; SHAM, sham-operated rats; SHL, sham rats fed a HFD; p-Akt/Akt
References
- Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9232-7 - PubMed
- Diabetes. 1967 Jan;16(1):35-9 - PubMed
- Int J Biochem Cell Biol. 2006 Feb;38(2):157-63 - PubMed
- Front Biosci (Landmark Ed). 2011 Jan 01;16:251-60 - PubMed
- Clin Sci (Lond). 2002 Feb;102(2):151-66 - PubMed
- Endocr Rev. 2013 Jun;34(3):309-38 - PubMed
- Semin Reprod Med. 2010 Sep;28(5):426-34 - PubMed
- J Physiol. 2011 May 15;589(Pt 10):2585-96 - PubMed
- Coron Artery Dis. 1998;9(8):503-11 - PubMed
- Diabetes. 1982 Sep;31(9):830-3 - PubMed
- Treat Endocrinol. 2005;4(2):95-114 - PubMed
- Diabetes Care. 2000 Jan;23(1):57-63 - PubMed
- J Immunol Methods. 1991 Jun 3;139(2):271-9 - PubMed
- Endocrinology. 2010 Mar;151(3):859-64 - PubMed
- J Clin Invest. 2004 Oct;114(7):928-36 - PubMed
- N Engl J Med. 1986 Dec 11;315(24):1519-24 - PubMed
- PLoS One. 2012;7(10):e47381 - PubMed
- Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2501-6 - PubMed
- Diabetes Obes Metab. 2012 Oct;14 Suppl 3:152-60 - PubMed
- Steroids. 2011 Dec 11;76(13):1425-32 - PubMed
- Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E192-8 - PubMed
- Diabetologia. 1981 Nov;21(5):470-5 - PubMed
- Endocrinology. 2005 Nov;146(11):4786-94 - PubMed
- Toxicol In Vitro. 2006 Oct;20(7):1106-13 - PubMed
- J Endocrinol. 1981 Jul;90(1):59-67 - PubMed
- J Clin Invest. 2002 Oct;110(7):1011-9 - PubMed
- Cell. 1999 Feb 5;96(3):329-39 - PubMed
- FEBS Lett. 2006 Jan 9;580(1):285-90 - PubMed
- Brain Res. 2010 Sep 2;1350:77-85 - PubMed
- Lipids. 1977 May;12(5):409-13 - PubMed
- Cell Metab. 2010 Dec 1;12(6):619-32 - PubMed
- Ann N Y Acad Sci. 1995 Dec 29;774:121-7 - PubMed
- Nat Rev Endocrinol. 2012 Feb 14;8(6):342-51 - PubMed
- Ginekol Pol. 2011 Sep;82(9):690-5 - PubMed
- Acta Physiol (Oxf). 2009 Nov;197(3):217-25 - PubMed
- Nutr J. 2009 Feb 17;8:11 - PubMed
- Ann Endocrinol (Paris). 2003 Apr;64(2):95-107 - PubMed
- Steroids. 2012 Aug;77(10):951-8 - PubMed
- Int J Obes Relat Metab Disord. 1997 Nov;21(11):1058-64 - PubMed
- Diabetes. 2000 Dec;49(12):2012-20 - PubMed
- Life Sci. 2004 Nov 19;76(1):57-70 - PubMed
- Diabetes. 2013 Jul;62(7):2157-63 - PubMed
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