DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet.
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.
Department of Physiology and Biophysics, ICB 1, USP, São Paulo, SP, Brazil.
Katherine
K
Veras
Department of Physiology and Biophysics, ICB 1, USP, São Paulo, SP, Brazil.
Felipe Natali
FN
Almeida
Department of Physiology and Biophysics, ICB 1, USP, São Paulo, SP, Brazil.
Renato Tadeu
RT
Nachbar
Department of Physiology and Biophysics, ICB 1, USP, São Paulo, SP, Brazil.
Daniel Simões
DS
de Jesus
Department of Physiology and Biophysics, ICB 1, USP, São Paulo, SP, Brazil.
João Paulo
JP
Camporez
Department of Physiology and Biophysics, ICB 1, USP, São Paulo, SP, Brazil.
Angelo Rafael
AR
Carpinelli
South African Medical Research Council and Department of Human Biology, University of Cape Town, Cape Town, South Africa.
Julia H
JH
Goedecke
Department of Physiology and Biophysics, ICB 1, USP, São Paulo, SP, Brazil.
Carla Roberta
CR
de Oliveira Carvalho
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