Berberine inhibits hepatic gluconeogenesis<i>via</i>the LKB1-AMPK-TORC2 signaling pathway in streptozotocin-induced diabetic rats

Jiang, Shujun; Li, Jingbin; Xu, Li; Zou, Xin; Wang, Kaifu; Lu, Fanghong; Yi, Ping

doi:10.3748/wjg.v21.i25.7777

Cited by 81 publications

(54 citation statements)

References 22 publications

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“…Both HSL and ATGL are phosphorylated by AMPK [16]. Studies have found that BBR regulated the metabolism of TG, cholesterol and glucose by regulating the expression of AMPK [17, 18]. In our study, the effects of BBR on p-HSL and ATGL were partially blocked by Compound C, which suggests that AMPK at least partially regulates the effects of BBR on p-HSL and ATGL.…”

Section: Discussionsupporting

confidence: 63%

Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway

et al. 2016

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BackgroundObesity is closely related to the metabolism of triacylglycerol (TG) in adipocytes. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are rate-limiting enzymes that control the hydrolysis of TG. Effects on ATGL and HSL to increase lipolysis may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicine plant Coptis chinensis. In the present study we show the effects of BBR on ATGL and HSL and explore the potential underlying mechanisms of these effects.MethodsThe TG content in cells was measured using a colorimetric assay. The expressions of HSL, ATGL and GPAT3 were evaluated by Western-blotting. The expression of ATGL was also evaluated by real-time PCR and radioimmunoassay. Compound C, an inhibitor of AMP-activated protein kinase (AMPK), was used to explore the possible pathway that involved in the effect of BBR on ATGL.ResultsTG content of differentiated 3T3-L1 cells was significantly decreased by more than 10% after treated with BBR. In differentiated 3T3-L1 adipocytes, BBR increased the expression of p-HSL and ATGL, and these effects were time-depended (p <0.01). The effect of BBR on ATGL expression could be abolished by Compound C which suggested that AMPK pathway was involved in the effects of BBR on p-HSL and ATGL.ConclusionsBBR could increase the expression of ATGL and therefore stimulate basal lipolysis in mature adipocytes through the associated mechanisms related to the AMPK pathway.

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Section: Discussionsupporting

confidence: 63%

Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway

et al. 2016

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“…TCDD was thought to reduce blood glucose in lab animals through an inhibition of gluconeogenesis (Viluksela et al, 1999). This could mimic some aspects of the anti-diabetic drugs such as metformin (Madiraju et al, 2014) and berbine (Jiang et al, 2015), as both have been shown to inhibit gluconeogenesis. However, this seemingly “beneficial” effect on blood glucose level does not negate the toxic profile of TCDD as demonstrated in our histopathological analysis in which severe liver damages were noted.…”

Section: Discussionmentioning

confidence: 99%

TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

Lefever

Chen

et al. 2016

Toxicology and Applied Pharmacology

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An increasing body of evidence has shown the important role of the gut microbiome in mediating toxicity following environmental contaminant exposure. The goal of this study was to determine if the adverse metabolic effects of chronic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure would be sufficient to exacerbate hyperglycemia, and to further determine if these outcomes were attributable to the gut microbiota alteration. Adult male CD-1 mice were exposed to TCDD (6 μg/kg body weight biweekly) by gavage and injected (i.p.) with STZ (4 × 50 mg/kg body weight) to induced hyperglycemia. 16S rRNA sequencing was used to characterize the changes in the microbiome community composition. Glucose monitoring, flow cytometry, histopathology, and organ characterization were performed to determine the deleterious phenotypic changes of TCDD exposure. Chronic TCDD treatment did not appear to exacerbate STZ-induced hyperglycemia as blood glucose levels were slightly reduced in the TCDD treated mice; however, polydipsia and polyphagia were observed. Importantly, TCDD exposure caused a dramatic change in microbiota structure, as characterized at the phylum level by increasing Firmicutes and decreasing Bacteroidetes while at the family level most notably by increasing Lactobacillaceae and Desulfovibrionaceae, and decreasing Prevotellaceae and ACK M1. The changes in microbiota were further found to be broadly associated with phenotypic changes seen from chronic TCDD treatment. In particular, the phylum level Bacteroidetes to Firmicutes ratio negatively correlated with both liver weight and liver pathology, and positively associated with %CD3+NK+ T cells, a key mediator of host-microbial interactions. Collectively, these findings suggest that the dysregulated gut microbiome may contribute to the deleterious effects (e.g., liver toxicity) seen with TCDD exposure.

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“…The anti-diabetic activity of Berberine was first reported in 1988 [36] and its activity has been tested in a number of animal and human studies. Berberine has been found to regulate blood glucose through multiple mechanisms: increasing glucokinase activity [37], increasing insulin secretion and islet regeneration [38], improving insulin resistance [39] and suppressing hepatic gluconeogenesis [40]. There are robust data showing that Berberine exhibits fewer side effects than western medicines in the majority of laboratory and clinical trials.…”

Section: Is There Experimental Evidence?mentioning

confidence: 99%

“…Moreover, Berberine can alleviate a variety of diabetic complications, including diabetic cardiovascular disease, type 2 diabetic nephropathy, and diabetic peripheral neuropathy [42]. The study by Jiang et al 2015 [40] compared the effects of Berberine, metformin and placebo control at the protein level in streptozotocininduced diabetic rats, and concluded that Berberine inhibited expression of the gluconeogenic proteins phosphor enolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) in the liver. Administration of Berberine to KKAy mice reduced FBG levels and Fins by changing the expression of many genes such as adenosine monophosphate-activated protein kinase-(AMPK-) p38, mitogen-activated protein kinase-glucose transporter 4 (MAPK-GLUT4), c-jun N-terminal kinase (JNK) pathway, and peroxisome proliferator-activated receptor α (PPARα) pathway, which was shown in the Zhang et al 2011 study [37].…”

Section: Is There Experimental Evidence?mentioning

confidence: 99%

Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis

Liang

Yin

et al. 2019

Endocr J

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We conducted a systematic review and meta-analysis to evaluate the effect of Berberine on glucose in patients with type 2 diabetes mellitus and identify potential factors may modifying the hypoglycemic effect. We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database to identify randomized controlled trials that investigated the effect of Berberine. We calculated weighted mean differences (WMD) and 95% confidence interval (CI) for fasting plasma glucose (FPG), postprandial plasma glucose (PPG) and glycated haemoglobin (HbA1c) levels. Twenty-eight studies were identified for analysis, with a total of 2,313 type 2 diabetes mellitus (T2DM) patients. The pool data showed that Berberine treatment was associated with a better reduction on FPG (WMD =-0.54 mmol/L, 95% CI:-0.77 to-0.30), PPG (WMD =-0.94 mmol/L, 95% CI:-1.27 to-0.61), and HbA1c (WMD =-0.54 mmol/L, 95% CI:-0.93 to-0.15) than control groups. Subgroup-analyses indicated that effects of Berberine on blood glucose became unremarkable as the treatment lasted more than 90 days, the daily dosage more than 2 g/d and patients aged more than 60 years. The efficiency of Berberine combined with hypoglycaemics is better than either Berberine or hypoglycaemic alone. The dosage and treatment duration of Berberine and patients' age may modify the effect.

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Berberine inhibits hepatic gluconeogenesisviathe LKB1-AMPK-TORC2 signaling pathway in streptozotocin-induced diabetic rats

Abstract: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway.

Cited by 81 publications

References 22 publications

Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway

Berberine increases adipose triglyceride lipase in 3T3-L1 adipocytes through the AMPK pathway

TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

Effects of berberine on blood glucose in patients with type 2 diabetes mellitus: a systematic literature review and a meta-analysis

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