Modulation of glucagon-like peptide-1 release by berberine: In vivo and in vitro studies

Yu, Yunli; Liu, Li; Wang, Xinting; Liu, Xiang; Liu, Xiaodong; Xie, Lin; Wang, Guangji

doi:10.1016/j.bcp.2009.11.017

Cited by 111 publications

(79 citation statements)

References 29 publications

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“…As Berberine is poorly absorbed into the bloodstream from the gut (Han et al 2011), the mechanism of its action is not clear, but modulation of gut microbiota and intestinal permeability are plausible possibilities that we wished to explore. Berberine stimulates GLP1 secretions (Yu et al 2010), and because GLP1 is co-released with GLP2 from intestinal L cells, it is possible that Berberine may be able to modulate GLP2 secretion. Therefore, in this study, we investigated the alterations of intestinal barrier and GLP2 secretion before and after Berberine treatment in type 2 diabetic rats, with the intention of establishing an association between Berberine's antidiabetic effects and intestinal permeability, endotoxemia, and GLP2 secretion.…”

mentioning

confidence: 99%

Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats

Shan¹,

Yang²,

Yang³

et al. 2013

Journal of Endocrinology

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For centuries, Berberine has been used in the treatment of enteritis in China, and it is also known to have anti-hyperglycemic effects in type 2 diabetic patients. However, as Berberine is insoluble and rarely absorbed in gastrointestinal tract, the mechanism by which it works is unclear. We hypothesized that it may act locally by ameliorating intestinal barrier abnormalities and endotoxemia. A high-fat diet combined with low-dose streptozotocin was used to induce type 2 diabetes in male Sprague Dawley rats. Berberine (100 mg/kg) was administered by lavage to diabetic rats for 2 weeks and saline was given to controls. Hyperinsulinemia and insulin resistance improved in the Berberine group, although there was no significant decrease in blood glucose. Berberine treatment also led to a notable restoration of intestinal villi/mucosa structure and less infiltration of inflammatory cells, along with a decrease in plasma lipopolysaccharide (LPS) level. Tight junction protein zonula occludens 1 (ZO1) was also decreased in diabetic rats but was restored by Berberine treatment. Glutamine-induced glucagon-like peptide 2 (GLP2) secretion from ileal tissue decreased dramatically in the diabetic group but was restored by Berberine treatment. Fasting insulin, insulin resistance index, plasma LPS level, and ZO1 expression were significantly correlated with GLP2 level. In type 2 diabetic rats, Berberine treatment not only augments GLP2 secretion and improves diabetes but is also effective in repairing the damaged intestinal mucosa, restoring intestinal permeability, and improving endotoxemia. Whether these effects are mechanistically related will require further studies, but they certainly support the hypothesis that Berberine acts via modulation of intestinal function.

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mentioning

confidence: 99%

Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats

Shan¹,

Yang²,

Yang³

et al. 2013

Journal of Endocrinology

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“…Hyperglycaemia causes excessive ROS formation, particularly superoxide anions (Jay et al, 2006), and ROS overproduction is involved in the development of beta cell dysfunction (Malin et al, 2014). Both clinical and experimental studies show that berberine is effective in treating the metabolic syndrome, correcting hyperinsulinaemia, increasing insulin sensitivity and stimulating insulin secretion through mechanisms including triglyceride reduction, augmented secretion of glucagon-like peptide (GLP)-2 and increased release of GLP-1 (Lu et al, 2009;Yu et al, 2010;Perez-Rubio et al, 2013;Shan et al, 2013). The berberine analogue, 8,8-dimethyldihydroberberine, improved glucose tolerance and alleviates insulin resistance in db/db mice (Cheng et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Uncoupling protein‐2 mediates the protective action of berberine against oxidative stress in rat insulinoma INS‐1E cells and in diabetic mouse islets

Liu

Gao

et al. 2014

British J Pharmacology

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Background and PurposeUncoupling protein‐2 (UCP2) may regulate glucose‐stimulated insulin secretion. The current study investigated the effects of berberine, an alkaloid found in many medicinal plants, on oxidative stress and insulin secretion through restoration of UCP2 expression in high glucose (HG)‐treated INS‐1E cells and rat islets or in db/db mouse islets.Experimental ApproachMouse and rat pancreatic islets were isolated. Nitrotyrosine, superoxide dismutase (SOD)‐1 and UCP2 expression and AMPK phosphorylation were examined by Western blotting. Insulin secretion was measured by elisa. Mitochondrial reactive oxygen species (ROS) production was detected by confocal microscopy.Key ResultsIncubation of INS‐1E cells and rat islets with HG (30 mmol·L−1; 8 h) elevated nitrotyrosine level, reduced SOD‐1 and UCP2 expression and AMPK phosphorylation, and inhibited glucose‐stimulated insulin secretion. HG also increased mitochondrial ROS in INS‐1E cells. Co‐treatment with berberine inhibited such effects. The AMPK inhibitor compound C, the UCP2 inhibitor genipin and adenovirus ucp2 shRNA inhibited these protective effects of berberine. Furthermore, compound C normalized berberine‐stimulated UCP2 expression but genipin did not affect AMPK phosphorylation. Islets from db/db mice exhibited elevated nitrotyrosine levels, reduced expression of SOD‐1 and UCP2 and AMPK phosphorylation, and decreased insulin secretion compared with those from db/m+ mice. Berberine also improved these defects in diabetic islets and genipin blocked the effects of berberine.Conclusions and ImplicationsBerberine inhibited oxidative stress and restored insulin secretion in HG‐treated INS‐IE cells and diabetic mouse islets by activating AMPK and UCP2. UCP2 is an important signalling molecule in mediating anti‐diabetic effects of berberine.

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“…The b-cell volume density corresponds to the ratio of insulin immunoreactivity area to pancreatic parenchymal area. The b-cell mass was calculated by multiplying the b-cell volume density by the weight of the pancreas (Yu et al 2010). The data from immunohistochemistry showed that high-dose GTS treatment significantly increased b-cell mass by 2.52-fold compared with DM rats (Fig.…”

Section: Plasma Glucose Insulin and Lipid Levelsmentioning

confidence: 99%

“…Glucagon-like peptide-1 (GLP1), secreted by enteroendocrine L-cells, is one of the most important incretins in the regulation of glucose homeostasis and insulin secretion (Baggio & Drucker 2007, Ranganath 2008. Our recent studies revealed that, berberine, another poorly absorbed natural product, may reduce blood glucose levels partly via stimulating GLP1 release , Yu et al 2010). This indicated that, similar to berberine, ginsenosides may exert antidiabetic activity via stimulating GLP1 secretion.…”

Section: Introductionmentioning

confidence: 99%

Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides

Liu

Zhang

et al. 2013

Journal of Endocrinology

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Panax ginseng is one of the most popular herbal remedies. Ginsenosides, major bioactive constituents in P. ginseng, have shown good antidiabetic action, but the precise mechanism was not fully understood. Glucagon-like peptide-1 (GLP1) is considered to be an important incretin that can regulate glucose homeostasis in the gastrointestinal tract after meals. The aim of this study was to investigate whether ginseng total saponins (GTS) exerts its antidiabetic effects via modulating GLP1 release. Ginsenoside Rb1 (Rb1), the most abundant constituent in GTS, was selected to further explore the underlying mechanisms in cultured NCI-H716 cells. Diabetic rats were developed by a combination of high-fat diet and low-dose streptozotocin injection. The diabetic rats orally received GTS (150 or 300 mg/kg) daily for 4 weeks. It was found that GTS treatment significantly ameliorated hyperglycemia and dyslipidemia, accompanied by a significant increase in glucose-induced GLP1 secretion and upregulation of proglucagon gene expression. Data from NCI-H716 cells showed that both GTS and Rb1 promoted GLP1 secretion. It was observed that Rb1 increased the ratio of intracellular ATP to ADP concentration and intracellular Ca 2C concentration. The metabolic inhibitor azide (3 mM), the K ATP channel opener diazoxide (340 mM), and the Ca 2C channel blocker nifedipine (20 mM) significantly reversed Rb1-mediated GLP1 secretion. All these results drew a conclusion that ginsenosides stimulated GLP1 secretion both in vivo and in vitro. The antidiabetic effects of ginsenosides may be a result of enhanced GLP1 secretion. Key Words" glucagon-like peptide-1 (GLP1)" ginsenosides " Rb1" type 2 diabetes " ginseng total saponins (GTS)

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Modulation of glucagon-like peptide-1 release by berberine: In vivo and in vitro studies

Cited by 111 publications

References 29 publications

Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats

Alteration of the intestinal barrier and GLP2 secretion in Berberine-treated type 2 diabetic rats

Uncoupling protein‐2 mediates the protective action of berberine against oxidative stress in rat insulinoma INS‐1E cells and in diabetic mouse islets

Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides

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