In vivo calcium regulation in diabetic skeletal muscle

In skeletal muscle, dysfunctional contractile activity has been linked to impaired intracellular Ca(2+) concentration ([Ca(2+)]i) regulation. Muscle force production is impaired and fatigability and muscle fragility deteriorate with diabetes. Use of a novel in vivo model permits investigation of [Ca(2+)]i homeostasis in diabetic skeletal muscle. Within this in vivo environment we have shown that diabetes perturbs the Ca(2+) regulatory system such that resting [Ca(2+)]i homeostasis following muscle contractions is compromised and elevations of [Ca(2+)]i are exacerbated. This review considers the impact of diabetes on the capacity of skeletal muscle to regulate [Ca(2+)]i, following muscle contractions and, in particular, the relationship between muscle fatigue and elevated [Ca(2+)]i in a highly ecologically relevant circulation-intact environment. Importantly, the role of mitochondria in calcium sequestration and the possibility that diabetes impacts this process is explored. Given the profound microcirculatory dysfunction in diabetes this preparation offers the unique opportunity to study the interrelationships among microvascular function, blood-myocyte oxygen flux and [Ca(2+)]i as they relate to enhanced muscle fatigability and exercise intolerance.