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J Appl Physiol (1985). 2018 Nov 15. doi: 10.1152/japplphysiol.00048.2018. [Epub ahead of print]

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

Author information

1
University of Juntendo, Japan.
2
Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Japan.
3
Physiology, Juntendo University Graduate School of Medicine, Japan.
4
Department of Pharmacology, Juntendo University School of Medicine, Japan.
5
Pharmacology, Juntendo University School of Medicine, Japan.
6
School of Medicine, Juntendo University, Japan.
7
Juntendo University Graduate School of Medicine, Japan.

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 weeks 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.

KEYWORDS:

[Ca2+] flux; contractile function; diabetes; exercise training; skeletal muscle

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