Lespedeza bicolor extract supplementation reduced hyperglycemia-induced skeletal muscle damage by regulation of AMPK/SIRT/PGC1?-related energy metabolism in type 2 diabetic mice

Abstract

Lespedeza bicolor (LB) is known to have antidiabetic activities; however, the underlying molecular mechanisms of LB in hyperglycemia-induced skeletal muscle damage is unclear. Inflammation and oxidative stress caused by type 2 diabetes mellitus (T2DM) not only contributes to insulin resistance, but also promotes muscle atrophy via decreased mus-cle protein synthesis and increased protein degradation, leading to frailty and sarcope-nia. In this study, we hypothesized that LB extract (LBE) supplementatin has an amelio-rative effect on hyperglycemia-induced skeletal muscle damage by activation of 5 ' adeno-sine monophosphate-activated protein kinase (AMPK)/sirtuin (SIRT)/proliferator-activated receptor gamma coactivator 1 alpha (PGC1 alpha )-associated energy metabolism in mice with T2DM. Dia-betes was induced by a high-fat diet with a 2-time streptozotoxin injection (30 mg/kg body weight) in male C57BL/6J mice. After diabetes was induced (fasting blood glucose level >140 mg/dL), the mice were administered with LBE at a low dose (100 mg/kg/d) or high dose (250 mg/kg/d) by gavage for 12 weeks. LBE supplementation ameliorated glucose tolerance and hemoglobin A1c (%) in mice with T2DM. Moreover, LBE supplementation upregulated pro-tein levels of insulin receptor subunit-1 and Akt accompanied by increased translocation of glucose transporter 4 in mice with T2DM. Furthermore, LBE increased mitochondrial bio-genesis by activating SIRT1, SIRT3, SIRT4, and peroxisome PGC1 alpha in diabetic skeletal mus-cle. Meanwhile, LBE supplementation reduced oxidative stress and inflammation in mice with T2DM. Taken together, the current study suggested that LBE could be a potential ther-apeutic to prevent skeletal muscle damage by regulation AMPK/SIRT/PGC1 alpha-related energy metabolism in T2DM.(c) 2022 Elsevier Inc. All rights reserved.