Berberine stimulates glucose transport through a mechanism distinct from insulin

Zhou, Libin; Yang, Ying; Xiao, Wang; Liu, Shangquan; Wang, Shang; Yuan, Guoyue; Li, Fengying; Tang, Junling; Chen, Ming-Dao; Chen, Jialun

doi:10.1016/j.metabol.2006.10.025

Cited by 160 publications

(107 citation statements)

References 32 publications

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“…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 inhibition of lipid synthesis in human hepatocytes (2).…”

supporting

confidence: 56%

Berberine improves glucose metabolism through induction of glycolysis

Yin¹,

Gao²,

Liu³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

332

221

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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...

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supporting

confidence: 56%

Berberine improves glucose metabolism through induction of glycolysis

Yin¹,

Gao²,

Liu³

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

332

221

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“…Berberine (BBR) is a naturally occurring structurally characterized compound present in many herbs and has a variety of pharmacological properties including glucose lowering (9,15,41) and antimicrobial activities (17). 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.…”

mentioning

confidence: 99%

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

Kim

Lee

Hun

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

204

143

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AMP-activated protein kinase (AMPK) plays an important role in regulating whole body energy homeostasis. Recently, it has been demonstrated that berberine (BBR) exerts antiobesity and antidiabetic effects in obese and diabetic rodent models through the activation of AMPK in peripheral tissues. Here we show that BBR improves lipid dysregulation and fatty liver in obese mice through central and peripheral actions. In obese db/db and ob/ob mice, BBR treatment reduced liver weight, hepatic and plasma triglyceride, and cholesterol contents. In the liver and muscle of db/db mice, BBR promoted AMPK activity and fatty acid oxidation and changed expression of genes involved in lipid metabolism. Additionally, intracerebroventricular administration of BBR decreased the level of malonyl-CoA and stimulated the expression of fatty acid oxidation genes in skeletal muscle. Together, these data suggest that BBR would improve fatty liver in obese subjects, which is probably mediated not only by peripheral AMPK activation but also by neural signaling from the central nervous system.

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“…Metformin and insulin stimulate glucose uptake in muscle cells by increasing GLUT 4 (Klip and Leiter, 1990). Berberine the reported active constituent of C. orbiculatus has been investigated to activate AMPK in skeletal muscle and adipose tissue that lead to increased glucose uptake (Yin et al, 2008;Cheng et al, 2006;Kim et al, 2007;Lee et al, 2006;Zhou et al, 2007; Mean ± SEM; n = 5; Groups II -VI were compared with Group I. a (p<0.05); b (p<0.01) Wang et al, 2004;Ko et al, 2005). Similarly gallic acid the constituent of L. india has been implicated to mediate insulin stimulated glucose transport in muscle and adipocytes (Vishnu Prasad et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of possible mechanisms of three plants for blood glucose control in diabetes

Dalu¹,

Dhulipala

2016

Bangladesh J Pharmacol

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This study was conducted to provide the evidence for the mechanism of antidiabetic activity of Cocculus orbiculatus, Leea indica and Ventilago maderaspatana. This was accomplished by employing methods like uptake of glucose, glycogen synthesis and inhibition of -glucosidase. For uptake of glucose, diaphragms were dissected out in Tyrode solution with 2% glucose and assayed for glucose content. In glycogen synthesis methodology liver, skeletal muscle and cardiac muscles were isolated, homogenized and glycogen content was analyzed. In -glucosidase enzyme inhibition procedure involved estimation of -glucosidase enzyme inhibition. All the three plant extracts exhibited significant (p<0.05 -p<0.01) anti-diabetic activity by increasing glucose uptake, glycogen synthesis and inhibiting -glucosidase enzyme. Among the three plants, V. maderaspatana (500 mg/kg) exhibited higher glucose uptake, glycogen content and -glucosidase inhibition activity (IC µg/mL). The present experimental results evidenced the anti-diabetic activity of three plants by all the three mechanisms. Article Info

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Berberine stimulates glucose transport through a mechanism distinct from insulin

Cited by 160 publications

References 32 publications

Berberine improves glucose metabolism through induction of glycolysis

Berberine improves glucose metabolism through induction of glycolysis

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

Evaluation of possible mechanisms of three plants for blood glucose control in diabetes

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