Berberine suppresses intestinal disaccharidases with beneficial metabolic effects in diabetic states, evidences from in vivo and in vitro study.
Clinical reports have demonstrated that berberine is a potential antidiabetic agent, but the underlying mechanism is unclear. The purpose of this study was to investigate if berberine exerts its hypoglycemic action via inhibiting intestinal disaccharidases using in vivo and in vitro experiments. Streptozotocin-induced diabetic rats received berberine (100 or 200 mg/kg) orally once daily or acarbose (40 mg/kg) orally twice daily for 5 weeks. Disaccharidase activities and sucrase-isomaltase (SI) complex messenger RNA (mRNA) expression in intestinal regions were assessed. The same treatment was operated in normal rats. Sucrose and maltose loading tests were also documented. In addition, Caco-2 cells were cultured in medium containing berberine or berberine plus chelerythrine. Compound C or H-89 for 5 days, disaccharidase activities, and SI complex mRNA levels were measured. The animal experiments showed that berberine significantly decreased the disaccharidase activities and SI complex mRNA expression both in diabetic rats and normal rats. Berberine can also significantly lower postprandial blood glucose levels induced by sucrose or maltose loading in normal rats. The cellular results showed that berberine may suppress disaccharidase activities and downregulate SI complex mRNA expression in a concentration-dependent manner. Only H-89, an inhibitor of protein kinase A (PKA), may reverse the decrease in disaccharidase activities and SI complex mRNA expression induced by berberine. In conclusion, berberine suppresses disaccharidase activities and SI complex mRNA expression with beneficial metabolic effects in diabetic states. The inhibitory effect, at least partly, involves the PKA-dependent pathway.
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Li
L
Liu
Yun-Li
YL
Yu
Jian-Song
JS
Yang
Yang
Y
Li
Yao-Wu
YW
Liu
Yan
Y
Liang
Xiao-Dong
XD
Liu
Lin
L
Xie
Guang-Ji
GJ
Wang
D020909:Acarbose / Q000494:pharmacology; D000818:Animals; D001599:Berberine / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D018938:Caco-2 Cells; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology; D004186:Disaccharidases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007422:Intestines / Q000201:enzymology; D008297:Male; D008320:Maltose / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D001599:Berberine; D013395:Sucrose; D013311:Streptozocin; D008320:Maltose; D017868:Cyclic AMP-Dependent Protein Kinases; D004186:Disaccharidases; D013394:Sucrase-Isomaltase Complex; D020909:Acarbose