Modulation of glucagon-like peptide-1 release by berberine: in vivo and in vitro studies

Biochem Pharmacol. 2010 Apr 1;79(7):1000-6. doi: 10.1016/j.bcp.2009.11.017. Epub 2009 Nov 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Berberine / pharmacology*
  • Blood Glucose / analysis
  • Body Weight / drug effects
  • Cells, Cultured
  • Eating / drug effects
  • Glucagon-Like Peptide 1 / metabolism*
  • Humans
  • Insulin / blood
  • Male
  • Proglucagon / genetics
  • Proprotein Convertase 1 / genetics
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley


  • Blood Glucose
  • Insulin
  • RNA, Messenger
  • Berberine
  • Proglucagon
  • Glucagon-Like Peptide 1
  • Proprotein Convertase 1