Diabetes-Induced Dysfunction of Mitochondria and Stem Cells in Skeletal Muscle and the Nervous System

Abstract

Diabetes mellitus is one of the most common metabolic diseases spread all over the world, which results in hyperglycemia caused by the breakdown of insulin secretion or insulin action or both. Diabetes has been reported to disrupt the functions and dynamics of mitochondria, which play a fundamental role in regulating metabolic pathways and are crucial to maintain appropriate energy balance. Similar to mitochondria, the functions and the abilities of stem cells are attenuated under diabetic condition in several tissues. In recent years, several studies have suggested that the regulation of mitochondria functions and dynamics is critical for the precise differentiation of stem cells. Importantly, physical exercise is very useful for preventing the diabetic alteration by improving the functions of both mitochondria and stem cells. In the present review, we provide an overview of the diabetic alterations of mitochondria and stem cells and the preventive effects of physical exercise on diabetes, focused on skeletal muscle and the nervous system. We propose physical exercise as a countermeasure for the dysfunction of mitochondria and stem cells in several target tissues under diabetes complication and to improve the physiological function of patients with diabetes, resulting in their quality of life being maintained.

Keywords: diabetes; exercise; mitochondria; neural stem cells; satellite cells.

Figure 1

Schematic representation of mitochondrial dysfunction in diabetic skeletal muscle. Skeletal muscle contains a large volume of mitochondria that produce energy for biological activity. Diabetes mellitus induces mitochondrial dysfunction, including decreased biogenesis, impaired quality control (e.g., fusion, fission and mitophagy), and excessive ROS production in skeletal muscle, leading to the reduction in mitochondrial content and oxidative phosphorylation.

Figure 2

Schematic representation of regulation of stem cell differentiation in skeletal muscle and the nervous systems. Skeletal muscle stem cells, termed satellite cells, are mainly in a quiescent state, but activated in response to muscle injury or exercise. Activated satellite cells can proliferate, differentiate into myoblasts, and then fuse and mature into myofibers. Diabetes mellitus impairs satellite cell activation and differentiation via inactivation of Wnt signaling and/or excessive oxidative stress, resulting in muscle atrophy and reduced oxidative capacity in skeletal muscle. In adult brain, neural stem cells (NSCs) give rise to neuroblasts, which differentiate into mature neuron. The progression of NSCs to mature neuron is controlled by Wnt and γ-aminobutyric acid (GABA). Diabetes inhibits the activation of Wnt signaling and the expression of GABA transporters, resulting in disturbed neurogenesis, which may be associated with cognitive deficits.