The anti-hyperglycemic efficacy of a lipid-lowering drug Daming capsule and the underlying signaling mechanisms in a rat model of diabetes mellitus.

Yong Zhang,Xiaohui Chen,Jiaming Ju,Xiaoguang Li,Jiamin Li,Xin Liu,Baofeng Yang,Haiying Zhang,Yingying Hu,Xianxian Wu,Huan Yang,Xin Li,Yue Zhang,Qingwei Zhang

doi:10.1038/srep34284

Abstract

Diabetes mellitus (DM) is a metabolic disorder manifested by hyperglycemia. Daming Capsule (DMC), a combination of traditional Chinese herbs, is used clinically as a lipid-lowering drug. This study was designed to evaluate if DMC possesses an anti-hyperglycemic effect and to elucidate the underlying mechanisms. Compared to diabetic rats, the rats received DMC (200 mg/kg/d) had significantly lower blood lipid and glucose levels. DMC markedly restored the decreased secretion of GLP-1 and GIP as well as the coding gene GCG and GIP in ileum. Moreover, DMC normalized depressed GCG and GIP transcription by significantly enhancing the GSK-3β/β-catenin signaling pathway and expression of TCF7L2, a transactivator of GCG and GIP in diabetic rats. DMC possesses an anti-hyperglycemic property characterized by preservation/stimulation of GLP-1 and GIP secretion in DM rats. Here, we proposed DMC → GSK-3β/β-catenin↑ → TCF7L2↑ → GLP-1, GIP secretion↑ → blood glucose↓ as a regulatory pathway of blood glucose homeostasis. Our findings suggest DMC as a promising therapeutic drug in the clinical treatment of diabetes.

Highlights

Parameter Body weight before Body weight Glucose before Glucose Water intake before Water intake after Food intake before Food intake after formulated in accordance with the TCM theory comprising several ingredients mainly including Rheum palmatum L. (Solanaceae), Cassia obtusifolia L., Salvia miltiorrhiza Bunge. (Labiatae), and Panax ginseng C
In diabetic rats induced by STZ and fed with the high-fat diet, the fasting blood glucose (FBG) levels increased significantly and glucose tolerance declined, accompanied by a decrease in body weight and an increase in food intake, indicating the successful establishment of diabetes with typical hyperglycemia (Table 1)
Our results showed that the ability of DMC to increase the expression of β-catenin and Transcription factor 7-like 2 (TCF7L2) was eliminated by inhibition of GSK-3βphosphorylation (Fig. 7E,F)

Summary

Introduction

Parameter Body weight before Body weight Glucose before Glucose Water intake before Water intake after Food intake before Food intake after formulated in accordance with the TCM theory comprising several ingredients mainly including Rheum palmatum L. (Solanaceae), Cassia obtusifolia L. (pulse family), Salvia miltiorrhiza Bunge. (Labiatae), and Panax ginseng C. Glucagon-like peptide-1 (GLP-1), an incretin hormone derived from the transcription of proglucagon gene (GCG), is released from the intestinal endocrine L cells in response to nutritional stimuli[12]. GLP-1 inhibits gastric secretion and regulates glucose homeostasis in the gastrointestinal tract after meals and is required for normal glucose tolerance[16,17]. The GSK-3β/β-catenin signaling pathway has a significant role on TCF7L2 transcription[27] These published studies allow for a formulization of GSK-3β/ β-catenin →TCF7L2 →GCG +GIP →blood glucose as a glucose homeostasis regulatory pathway[26]. The present study aimed to examine this notion by investigating whether DMC possesses an anti-hyperglycemic property, in addition to its well-established anti-hyperlipidemic effect, and to decipher the underlying mechanisms of DMC in a rat model of diabetes mellitus

Methods

Results

Conclusion