Dysfunction of muscle contraction with impaired intracellular Ca2+handling in skeletal muscle and the effect of exercise training in maledb/dbmice
- 1 January 2019
- journal article
- research article
- Published by American Physiological Society in Journal of Applied Physiology
- Vol. 126 (1), 170-182
- https://doi.org/10.1152/japplphysiol.00048.2018
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
Funding Information
- KAKENHI (16J11193, 15H06597)
- Suzuken Memorial Foundation
- Strategic Research Foundation at Private Universities
This publication has 65 references indexed in Scilit:
- Muscle lipogenesis balances insulin sensitivity and strength through calcium signalingJCI Insight, 2013
- Heterogeneity Among White Adipose Tissue Depots in Male C57BL/6J MiceObesity, 2012
- Ryanodine Receptor Oxidation Causes Intracellular Calcium Leak and Muscle Weakness in AgingCell Metabolism, 2011
- Sex differences in intracellular Ca2+ accumulation following eccentric contractions of rat skeletal muscle in vivoAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2010
- Interval Training Normalizes Cardiomyocyte Function, Diastolic Ca 2+ Control, and SR Ca 2+ Release Synchronicity in a Mouse Model of Diabetic CardiomyopathyCirculation Research, 2009
- Sarcalumenin is essential for maintaining cardiac function during endurance exercise trainingAmerican Journal of Physiology-Heart and Circulatory Physiology, 2009
- Excessive Loss of Skeletal Muscle Mass in Older Adults With Type 2 DiabetesDiabetes Care, 2009
- Exercise training during diabetes attenuates cardiac ryanodine receptor dysregulationJournal of Applied Physiology, 2009
- Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscleNature Medicine, 2009
- The influence of age and dietary conditions on diabetes in the db mouseDiabetologia, 1970