Molecular basis of the regulation of muscle stem cell activation, proliferation and differentiation in diabetes mellitus

Abstract

Diabetes mellitus is a chronic disease still without curative treatment. Diabetes type 1 occurs when insulin production is deficient in pancreas, although diabetes type 2 is characterized by impairment on insulin action in peripheral tissues (as skeletal muscle, liver and adipose tissue) associated to deficient insulin secretion by beta cells. The skeletal muscle has an important role in plasma glucose uptake and preservation of muscle mass is crucial to maintain glycemic homeostasis. Evidences suggest a possible impairment on muscle stem cell function in diabetes mellitus. Muscle stem cells (or satellite cells) are responsible for repair of muscle tissue and maintaining muscle mass in response to stressful stimuli such as exercise, mechanical overload and injury. The failure in wound repair is a well described feature of diabetes mellitus. Evidence indicates that muscle regeneration is also impaired in diabetic animals suggesting a possible dysfunction of muscle stem cells due to diabetic state. The objective of this project is to evaluate the impact of diabetic state on muscle stem cell function (activation, proliferation, differentiation and regenerative capacity). For this, the activation, proliferation and differentiation of muscle stem cells will be assessed in vivo after muscle injury. The proliferation and differentiation of muscle stem cells from diabetic animals will be also evaluated in vitro and also assessed in favorable culture conditions (culture medium with fetal bovine serum) and diabetic medium (consisted of culture medium with serum extracted from diabetic animals). The regenerative capacity of muscle stem cells from diabetic animals will be also evaluated through regeneration of injured muscle after stem cell transplantation in non-diabetic syngeneic animals.