Berberine acutely inhibits insulin secretion from beta-cells through 3',5'-cyclic adenosine 5'-monophosphate signaling pathway.
Berberine, a hypoglycemic agent, has recently been shown to activate AMP-activated protein kinase (AMPK) contributing to its beneficial metabolic effects in peripheral tissues. However, whether berberine exerts a regulatory effect on beta-cells via AMPK or other signaling pathways and counteracts glucolipotoxicity remains uncertain. In the present study, the impact of berberine on beta-cell function was investigated in vivo and in vitro. In high-fat-fed rats, berberine treatment for 6 wk significantly decreased plasma glucose and insulin levels before and after an oral glucose challenge along with the reduction of body weight and improvement of blood lipid profile. In accordance with the in vivo results, berberine acutely decreased glucose-stimulated insulin secretion (GSIS) and palmitate-potentiated insulin secretion in MIN6 cells and rat islets. However, pretreated with berberine for 24 h augmented the response of MIN6 cells and rat islets to glucose and attenuated the glucolipotoxicity. Berberine acutely increased AMPK activity in MIN6 cells. However, compound C, an AMPK inhibitor, completely reversed troglitazone-suppressed GSIS, not berberine-suppressed GSIS. Otherwise, berberine decreased cAMP-raising agent-potentiated insulin secretion in MIN6 cells and rat islets. These results suggest that the activation of AMPK is required for troglitazone-suppressed GSIS, whereas cAMP signaling pathway contributes, at least in part, to the regulatory effect of berberine on insulin secretion.
Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai 200025, People's Republic of China.
Libin
L
Zhou
Xiao
X
Wang
Li
L
Shao
Ying
Y
Yang
Wenbin
W
Shang
Guoyue
G
Yuan
Boren
B
Jiang
Fengying
F
Li
Jingfeng
J
Tang
Hua
H
Jing
Mingdao
M
Chen
D055372:AMP-Activated Protein Kinases; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004036:Diet, Atherogenic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D004791:Enzyme Inhibitors; D007328:Insulin; D009097:Multienzyme Complexes; D001599:Berberine; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D055372:AMP-Activated Protein Kinases