Protective Effect of Jiang Tang Xiao Ke Granules against Skeletal Muscle IR via Activation of the AMPK/SIRT1/PGC-1α Signaling Pathway.

Ying Bai,Dongwei Zhang,Tian Tian,Dandan Zhao,Qianqian Mu,Rufeng Ma,Fangfang Mo,Yi Zhang,Sihua Gao,Jiacheng Zuo,Xin Fang,Xueli Bao,Na Yu,Antonella Smeriglio

doi:10.1155/2021/5566053

Abstract

The Jiang Tang Xiao Ke (JTXK) granule is a classic Chinese herbal formula that has been put into clinical use in the treatment of type 2 diabetes mellitus for decades. However, whether its ability to ameliorate skeletal muscle insulin resistance (IR) is through modulation of the AMPK/SIRT1/PGC-1α signaling pathway remains unknown. Therefore, we aimed to investigate the effects of JTXK granules on IR in skeletal muscle of high-fat diet-induced diabetic mice and C2C12 cells and analyze the underlying mechanisms. In the present study, we showed that JTXK granules attenuated body weight gain, reduced body fat mass, improved body lean mass, and enhanced muscle performance of diabetic mice. JTXK granules also improved glucose metabolism and skeletal muscle insulin sensitivity and partially reversed abnormal serum lipid levels, which might be related to the regulation of the AMPK/SIRT1/PGC-1α pathway, both in skeletal muscle tissue of diabetic mice and in C2C12 cells. Furthermore, drug-containing serum of JTXK granules was capable of enhancing glucose uptake and mitochondrial respiration in C2C12 cells, and AMPKα was proven to be closely involved in this process. Taken together, these results suggest that the JTXK granule ameliorates skeletal muscle IR through activation of the AMPK/SIRT1/PGC-1α signaling pathway, which offers a novel perspective of this formula to combat IR-related metabolic diseases.

Highlights

Insulin resistance (IR) is a heterogeneous metabolic defect that primarily refers to the abnormality of insulinmediated glucose disposal [1]
There were lipid droplets and swelling mitochondria in the skeletal muscle tissue, while these pathological changes were ameliorated in Met and Jiang Tang Xiao Ke (JTXK) groups
(4) The JTXK granule was capable of enhancing glucose uptake and mitochondrial respiration in C2C12 cells, and AMPKα was proven to be closely involved in this process

Summary

Introduction

Insulin resistance (IR) is a heterogeneous metabolic defect that primarily refers to the abnormality of insulinmediated glucose disposal [1]. IR is the main characteristic of obesity or type 2 diabetes mellitus (T2DM) and the promoter of these metabolic diseases [2]. Skeletal muscle, accounting for the largest portion of insulin-mediated glucose uptake, utilization, and storage, is crucial in metabolic disorders [3, 4]. Enormous evidence has shown that mitochondrial dysfunction in skeletal muscle tissue plays an essential role in impaired insulin signaling. A reduced rate of mitochondrial ATP synthesis was observed in skeletal muscle of obese patients, prediabetic patients, and offspring of diabetic patients [5, 6]. Longterm hyperglycemia and hyperlipidemia lead to mitochondrial impairment [7], and mitochondrial dysfunction in turn will aggravate glucolipid metabolic disorder [8]. Maintaining the functional integrity of skeletal muscle mitochondria is considered an important approach

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