Impact of Diabetes Mellitus and Associated Changes on Skeletal Muscle and its Stem Cell Population

Abstract

Diabetes Mellitus is chronic lifelong condition that continues to be a global health concern. Despite the development of insulin therapy in 1921, many diabetics are likely to endure a number of co-morbidities that impact their quality of life. Today, the search for additional diabetic therapies incorporates the investigation of various organ systems for their potential in attenuating disease development. Skeletal muscle is a striated tissue that is integral to metabolism, movement, and overall wellbeing, yet its significance to Diabetes Mellitus remains understudied, as compared to other metabolic tissues. Previous work has identified that diabetes promotes adverse changes to skeletal muscle physiology, function, and morphology, contributing to a complication referred to as diabetic myopathy. The capacity to adapt to changing internal and external cues, as achieved through skeletal muscle plasticity, permits the maintenance of skeletal muscle health; a term encompassing its metabolism, function, and/or structure. This malleability is primarily regulated by the function of muscle progenitor stem cells, referred to as satellite cells. While past research has shown that satellite cells are hindered in various diabetic states, the precise mechanisms through which these observations occur remain to be elucidated. The data presented herein identify impaired satellite cell activation in two sub-types of diabetes (Pre-Diabetes and Type 1 Diabetes), and shows that such results are mediated by alterations to intrinsic signalling cascades. Additional insight into a potential unifying mechanism mediating this response led to the identification of Lipocalin-2 and its influence on satellite cell function and muscle plasticity. The results uncovered in these studies have enhanced our understanding of the response of satellite cells in diabetes, and have identified a prospective therapeutic target for the attenuation of diabetic myopathy.