Dehydroepiandrosterone sulfate and beta-cell function: enhanced glucose-induced insulin secretion and altered gene expression in rodent pancreatic beta-cells.
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.
Dillon
J S
JS
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA. joseph-dillon@uiowa.edu
Yaney
G C
GC
Zhou
Y
Y
Voilley
N
N
Bowen
S
S
Chipkin
S
S
Bliss
C R
CR
Schultz
V
V
Schuit
F C
FC
Prentki
M
M
Waxman
D J
DJ
Corkey
B E
BE
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
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