Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine

Abstract

BackgroundBerberine is known to improve glucose and lipid metabolism disorders, but it poorly absorbed into the blood stream from the gut. Therefore, the exact underlying mechanism for berberine is still unknown. In this study, we investigated the effect of berberine on glucose metabolism in diabetic rats and tested the hypothesis that berberine acts directly in the terminal ileums.MethodsRats were divided into a control group, diabetic group (DM), low dose of berberine group (BerL) and high dose of berberine group (BerH). Ileum samples were analyzed using a Roche NimbleGen mRNA array, qPCR and immunohistochemistry.ResultsWe found that 8 weeks of treatment with berberine significantly decreased fasting blood glucose levels. An oral glucose tolerance test (OGTT) showed that blood glucose was significantly reduced in the BerL and BerH groups before and at 30 min, 60 min and 120 min after oral glucose administration. Plasma postprandial glucagon-like peptide-1 (GLP-1) levels were increased in the berberine-treated groups. The ileum from the BerH group had 2112 genes with significantly changed expression (780 increased, 1332 decreased). KEGG pathway analyses indicated that all differentially expressed genes included 9 KEGG pathways. The top two pathways were the MAPK signaling pathway and the GnRH signaling pathway. Q-RT-PCR and immunohistochemistry verified that glucagon-like peptide 1 receptor (Glp1r) and mitogen activated protein kinase 10 (Mapk10) were significantly up-regulated, in contrast, gonadotropin releasing hormone receptor (Gnrhr) and gonadotropin-releasing hormone 1 (Gnrh1) were down-regulated in the BerH group.ConclusionOur data suggest that berberine can improve blood glucose levels in diabetic rats. The mechanisms involved may be in the MAPK and GnRh-Glp-1 pathways in the ileum.

Erchen Decoction and Linguizhugan Decoction Ameliorate Hepatic Insulin Resistance by Inhibiting IRS‐1Ser307 Phosphorylation In Vivo and In Vitro

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Dual‐Stimuli‐Responsive Gut Microbiota‐Targeting Berberine‐CS/PT‐NPs Improved Metabolic Status in Obese Hamsters

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Identification and Verification of Potential Therapeutic Target Genes in Berberine-Treated Zucker Diabetic Fatty Rats through Bioinformatics Analysis

“…The main form of diabetes found in 90~95% of diabetic patients globally is type 2 diabetes mellitus (T2DM) [2]. Diabetes can cause many complications, including neuropathy, nephropathy and retinopathy [3]. Diabetes seriously affects the quality of life of patients.…”

“…The anti-diabetes activity of Rhizoma Coptidis was documented in the book “Notes of Elite Physicians” written by Hongjing Tao 1500 years ago [3, 4]. Berberine (BBR) is the major isoquinoline alkaloid constituent of the Chinese herb Rhizoma Coptidis [1,5,6,7], which has the beneficial characteristic of regulating glucose and lipid metabolism and has been extensively used in the treatment of obesity, diabetes and hypercholesterolemia [3].…”

“…Berberine (BBR) is the major isoquinoline alkaloid constituent of the Chinese herb Rhizoma Coptidis [1,5,6,7], which has the beneficial characteristic of regulating glucose and lipid metabolism and has been extensively used in the treatment of obesity, diabetes and hypercholesterolemia [3]. Zucker diabetic fatty (ZDF) rats are an animal model of type 2 diabetes mellitus due to a leptin receptor gene mutation.…”