Dysfunction of muscle contraction with impaired intracellular Ca2+ handling in skeletal muscle and the effect of exercise training in male db/db mice

Abstract

Type 2 diabetes is characterized by reduced contractile force production and increased fatigability of skeletal muscle. While the maintenance of Ca²⁺ homeostasis during muscle contraction is a requisite for optimal contractile function, the mechanisms underlying muscle contractile dysfunction in type 2 diabetes are unclear. Here, we investigated skeletal muscle contractile force and Ca²⁺ flux during contraction and pharmacological stimulation in type 2 diabetic model mice ( db/db mice). Furthermore, we investigated the effect of treadmill exercise training on muscle contractile function. In male db/db mice, muscle contractile force and peak Ca²⁺ levels were both lower during tetanic stimulation of the fast-twitch muscles, while Ca²⁺ accumulation was higher after stimulation compared with control mice. While 6 wk of exercise training did not improve glucose tolerance, exercise did improve muscle contractile dysfunction, peak Ca²⁺ levels, and Ca²⁺ accumulation following stimulation in male db/db mice. These data suggest that dysfunctional Ca²⁺ flux may contribute to skeletal muscle contractile dysfunction in type 2 diabetes and that exercise training may be a promising therapeutic approach for dysfunctional skeletal muscle contraction. NEW & NOTEWORTHY The purpose of this study was to examine muscle contractile function and Ca²⁺ regulation as well as the effect of exercise training in skeletal muscle in obese diabetic mice ( db/db). We observed impairment of muscle contractile force and Ca²⁺ regulation in a male type 2 diabetic animal model. These dysfunctions in muscle were improved by 6 wk of exercise training.