title: Dehydroepiandrosterone sulfate and beta-cell function: enhanced glucose-induced insulin secretion and altered gene expression in rodent pancreatic beta-cells.
abstract: Administration of dehydroepiandrosterone (DHEA), or its sulfated form (DHEAS), controls hyperglycemia in diabetic rodents without directly altering insulin sensitivity. We show that DHEAS enhanced glucose-stimulated insulin secretion when administered in vivo to rats or in vitro to beta-cell lines, without changing cellular insulin content. Insulin secretion increased from 3 days of steroid exposure in vitro, suggesting that DHEAS did not directly activate the secretory processes. DHEAS selectively increased the beta-cell mRNA expression of acyl CoA synthetase-2 and peroxisomal acyl CoA oxidase in a time-dependent manner. Although DHEAS is a peroxisomal proliferator, it did not alter the mRNA expression of peroxisomal proliferator-activated receptor (PPAR) alpha or beta, or enhance the activity of transfected PPAR alpha, beta, or gamma in vitro. Thus, DHEAS directly affected the beta-cell to enhance glucose-stimulated insulin secretion and increased the mRNA expression of specific beta-cell mitochondrial and peroxisomal lipid metabolic enzymes. This effect of DHEAS on insulin secretion may contribute to the amelioration of hyperglycemia seen in various rodent models of diabetes.
authors: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA. joseph-dillon@uiowa.edu
authors: J S
authors: JS
authors: Dillon
authors: G C
authors: GC
authors: Yaney
authors: Y
authors: Y
authors: Zhou
authors: N
authors: N
authors: Voilley
authors: S
authors: S
authors: Bowen
authors: S
authors: S
authors: Chipkin
authors: C R
authors: CR
authors: Bliss
authors: V
authors: V
authors: Schultz
authors: F C
authors: FC
authors: Schuit
authors: M
authors: M
authors: Prentki
authors: D J
authors: DJ
authors: Waxman
authors: B E
authors: BE
authors: Corkey
mesh_terms: D042962:Acyl-CoA Oxidase; D000818:Animals; D002460:Cell Line; D003066:Coenzyme A Ligases / Q000235:genetics; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D024101:Mitochondrial Proteins; D010088:Oxidoreductases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D007328:Insulin; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D019314:Dehydroepiandrosterone Sulfate; D010088:Oxidoreductases; C107176:peroxisomal acyl-CoA oxidase; D042962:Acyl-CoA Oxidase; D003066:Coenzyme A Ligases; C115795:acyl CoA synthetase 5; C508147:Acsl5 protein, rat; D005947:Glucose