Berberine improves glucose metabolism through induction of glycolysis

Abstract

Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48%, respectively, in the rats. In cell lines including 3T3-L1 adipocytes, L6 myotubes, C2C12 myotubes, and H4IIE hepatocytes, berberine was found to increase glucose consumption, 2-deoxyglucose uptake, and to a less degree 3-O-methylglucose (3-OMG) uptake independently of insulin. The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser 307/312 ), Akt, p70 S6, and ERK phosphorylation. AMPK phosphorylation was increased by berberine at 0.5 h, and the increase remained for Ն16 h. Aerobic and anaerobic respiration were determined to understand the mechanism of berberine action. The long-lasting phosphorylation of AMPK was associated with persistent elevation in AMP/ATP ratio and reduction in oxygen consumption. An increase in glycolysis was observed with a rise in lactic acid production. Berberine exhibited no cytotoxicity, and it protected plasma membrane in L6 myotubes in the cell culture. These results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. Berberine-induced AMPK activation is likely a consequence of mitochondria inhibition that increases the AMP/ATP ratio. type 2 diabetes; insulin sensitivity; oxygen consumption; mitochondrial function; adenosine 5Ј-monophosphate-activated protein kinase BERBERINE IS A BOTANICAL ALKALOID in the roots and bark of several plants, including Coptis chinensis French, an ancient Chinese herb that has been used to treat diabetes for thousands of years in China. Berberine is the main active compound of the herb. In addition to its metabolic activities, berberine has well-established antimicrobial activities in the control of infection by bacteria, viruses, fungi, protozoans, and helminthes (8,14). It is an over-the-counter drug for the treatment of gastrointestinal infections in China. In 1988, the hypoglycemic effect of berberine was found when berberine was used to treat diarrhea in diabetic patients in China (13). Since then, berberine has been used as an antihyperglycemic agent by many physicians in China. There are many clinical reports about the hypoglycemic action of berberine in Chinese literature.Regarding the mechanism of berberine action, we found that berberine increased glucose metabolism in cultured cells, and this activity was comparable to that observed for metformin in 2002 (20). This activity was confirmed later in other studies, and AMPK was proposed to mediate the metabolic activities of berberine (2, 3, 9, 22). In 2006, it was reported that berberine was able to activate AMPK for inh...

Berberine improves lipid dysregulation in obesity by controlling central and peripheral AMPK activity

“…Intraperitoneal administration of BBR into obese db/db mice reduced body weight without a significant effect on food intake ( Fig. 1, A and B), which is consistent with previous reports (5,9,16,19,38). In addition, we observed that BBR lowered the RQ ratio and increased energy expenditure (Fig.…”

“…We and others (9,19,38) have reported that BBR reduces body weight, causes a significant improvement in glucose tolerance, and improves insulin action in obese and/or diabetic subjects by activating AMPK. A large body of evidence indicates that BBR enhances insulin sensitivity and reduces hyperlipidemia (5,9,16,38). Thus it is plausible to speculate that this mechanism might be applied therapeutically to treat fatty liver and hyperlipidemia.…”

Pentamethylquercetin generates beneficial effects in monosodium glutamate-induced obese mice and C2C12 myotubes by activating AMP-activated protein kinase

“…The glucose concentration in medium was determined by the glucose oxidase method after 24 h of treatment. The glucose concentration of the wells with cells was subtracted from the glucose concentration of the blank wells to obtain the amount of glucose consumption [28].…”

Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity

“…Previous studies have demonstrated t h a t b e r b e r i n e m o d u l a t e s ch o l e s t e r o l t h r o u g h increasing low-density lipoprotein receptor mRNA stability [4] , reduces body adiposity and increases insulin sensitivity partly through activating AMP-activated protein kinase [5] , and improves glucose metabolism via induction of glycolysis [6] , implying a promising future for berberine in the therapy of diabetes. Moreover, a new research further revealed that berberine also possessed insulinotropic property in isolated pancreatic islets [7] .…”