Troglitazone acutely activates AMP-activated protein kinase and inhibits insulin secretion from beta cells.
Changes in AMP-activated protein kinase (AMPK) activity contribute to the regulation of insulin secretion. Troglitazone has been shown to lower serum insulin levels and protect beta cell function. The aim of the present study was to examine the effects of troglitazone on AMPK activity and insulin secretion in beta cells. Isolated rat islets and MIN6 cells were treated for a short (1 h) or a long time (20 h) with troglitazone. One-hour troglitazone treatment activated AMPK and inhibited both glucose-stimulated insulin secretion (GSIS) and the response of insulin secretion to combined stimuli of glucose and palmitate. Long (20 h) treatment with troglitazone caused a sustained phosphorylation of AMPK and acetyl-CoA carboxylase, and increased GSIS after withdrawal of the drug. This study provided evidence that troglitazone activated AMPK in beta cells. In addition to the insulin-sensitizing effects in peripheral tissues, troglitazone also directly inhibits insulin hypersecretion by the elevated glucose and fatty acids, and thus protects beta cells from glucolipotoxicity.
Wang
Xiao
X
Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Zhou
Libin
L
Shao
Li
L
Qian
Lei
L
Fu
Xuelian
X
Li
Guo
G
Luo
Tianhong
T
Gu
Yanyun
Y
Li
Fengying
F
Li
Jiping
J
Zheng
Sheng
S
Luo
Min
M
D000818:Animals; D002460:Cell Line; D002839:Chromans / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015151:Immunoblotting; D007202:Indicators and Reagents; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010168:Palmitates / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007202:Indicators and Reagents; D007328:Insulin; D010168:Palmitates; D045162:Thiazolidinediones; D017868:Cyclic AMP-Dependent Protein Kinases; D000077288:Troglitazone; D005947:Glucose