Modulation of Skeletal Muscle Performance and SERCA by Exercise and Adiponectin Gene Therapy in Insulin-Resistant Rat

Abstract

This study addresses the potential application of adiponectin gene therapy and exercise in protection against skeletal muscle dysfunction in type 2 diabetes mellitus (T2DM) while focusing on the role of sarco and endoplasmic reticulum Ca(+2) ATPase (SERCA) and Glut4. 50 rats were divided into five groups: control, T2DM, T2DM treated with either adiponectin gene or exercise or a combination of both. Serum glucose, insulin, HOMA index, triglycerides, and cholesterol were measured. Weight gain%, muscle contractile parameters {(peak twitch tension (Pt), peak tetanic tension (PTT), half relaxation time (HRT)}, and gene expression of SERCA, Glut4, and adiponectin were assessed in gastrocnemius muscle. Diabetic rats treated with either adiponectin gene or exercise showed significant reduction in all serum parameters and wt gain%. There was significant elevation in Pt and PTT with shortening in HRT. Furthermore, a significant increase in SERCA, Glut4, and adiponectin gene expression was noticed in both groups. Combination therapy caused marked gene expression of SERCA, GLUT4, and greater improvement in muscle contractility than either of the monotherapies. Skeletal muscle dysfunction in T2DM is mediated via impaired SERCA and Glut 4. Combination therapy offered best protection against muscle dysfunction and provides a novel promising strategy for a complete cure of muscle dysfunction in T2DM.