Modulation of glucagon-like peptide-1 release by berberine: in vivo and in vitro studies.
Glucagon-like peptide (GLP)-1 is a potent glucose-dependent insulinotropic gut hormone released from intestinal L cells. Our previous studies showed that berberine increased GLP-1 secretion in streptozotocin-induced diabetic rats. The aim of this study was to investigate whether berberine affected GLP-1 release in normal rats and in NCI-H716 cells. Proglucagon and prohormone convertase 3 genes regulating GLP-1 biosynthesis were analyzed by RT-PCR. Effects of pharmacological inhibitors on berberine-mediated GLP-1 release were studied. In vivo, 5-week treatment of berberine enhanced GLP-1 secretion induced by glucose load and promoted proglucagon mRNA expression as well as L cell proliferation in intestine. In vitro, berberine concentration-dependently stimulated GLP-1 release in NCI-H716 cells. Berberine also promoted both prohormone convertase 3 and proglucagon mRNA expression. Chelerythrine (inhibitor of PKC) concentration-dependently suppressed berberine-mediated GLP-1 secretion. Compound C (inhibitor of AMPK) also inhibited berberine-mediated GLP-1 secretion. But only low concentrations of H89 (inhibitor of PKA) showed inhibitory effects on berberine-mediated GLP-1 release. The present results demonstrated that berberine showed its modulation on GLP-1 via promoting GLP-1 secretion and GLP-1 biosynthesis. Some signal pathways including PKC-dependent pathway were involved in this process. Elucidation of mechanisms controlling berberine-mediated GLP-1 secretion may facilitate the understanding of berberine's antidiabetic effects.
Yu
Yunli
Y
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, PR China. chrisyu1255@hotmail.com
Liu
Li
L
Wang
Xinting
X
Liu
Xiang
X
Liu
Xiaodong
X
Xie
Lin
L
Wang
Guangji
G
D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004435:Eating / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D052336:Proglucagon / Q000235:genetics; D045664:Proprotein Convertase 1 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D001599:Berberine; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D045664:Proprotein Convertase 1