[dek]A Discovery of Molecular Mechanisms
Zhang B, Pan Y, Xu L, Tang D, Dorfman RG, Zhou Q, Yin Y, Li Y, Zhou L, Zhao S, Zou X, Wang L, and Zhang M. “Berberine Promotes Glucose Uptake and Inhibits Gluconeogenesis By Inhibiting Deacetylase Sirt3.” Endocrine 62, no. 3 (2018): 576–87.
Berberine is one of the most widely recommended plant compounds to support healthy blood sugar and lipid balance.* Previous studies have found that berberine acts by stimulating cellular glucose uptake and reducing hepatic glucose output. The details of its mechanisms of action at the cellular and molecular level, however, remain unclear.
Researchers have proposed that one way that berberine might act is by influencing sirtuin 3 (SIRT3)—a protein in the mitochondrial matrix. SIRT3 coordinates mitochondrial respiration and ATP production.
This study explores new mechanisms by which berberine might influence glucose metabolism via SIRT3.
This is an in vitro cell study, using hepatocytes from mice. Researchers assessed the effects of berberine on SIRT3, as well as downstream signaling pathways, through immunoblotting and metabolic monitoring.
Berberine was found to inhibit SIRT3, leading to inhibition of Complex 1 in the electron transport chain and accumulation of adenosine monophosphate (AMP).
The increased ratio of AMP to ATP activated the AMP-activated protein kinase (AMPK) signaling pathway. This pathway promotes cellular glucose uptake, which is a previously established effect of berberine.
The accumulation of AMP that resulted from SIRT3 inhibition had a second and independent effect: It also led to the degradation of phosphoenolpyruvate carboxykinase 1 (PEPCK1). PEPCK1 is a critical enzyme for gluconeogenesis, so hepatic glucose production was blocked.
Numerous human clinical trials have demonstrated a role for berberine in supporting healthy metabolism. A meta-analysis of 14 trials involving 1068 participants concluded that berberine supplementation supports healthy glucose and lipid metabolism, especially when combined with lifestyle changes such as diet and exercise.*
Clinical trials published in recent years continue to show that berberine supports healthy weight management, healthy blood pressure, healthy lipid metabolism, and healthy blood sugar balance.*
A 2015 randomized controlled trial reported that berberine went mainly to the liver after absorption, with hepatic concentrations 50 times that of serum. Berberine also upregulated the expression of hepatic genes related to metabolism for up to 48 hours after ingestion.*
Previous mechanistic studies have found that berberine supports expression of cellular insulin receptors and production of glucagon-like peptide-1 (GLP-1). Studies have also shown that berberine modulates cytochrome P450 hepatic enzymes.*
The current study describes additional cellular mechanisms by which berberine acts to regulate glucose metabolism. For the first time, berberine was shown to inhibit SIRT3, which leads to upregulation of AMPK and the subsequent uptake of glucose into cells. SIRT3 inhibition also leads to degradation of PPCK1 and the subsequent inhibition of gluconeogenesis.*
Most human clinical trials show that berberine benefits metabolic health at intakes of 500 mg taken three times per day. Always check for potential nutrient or drug interactions when recommending berberine for metabolic support.*
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