Mitochondrial Impairment in Muscle Insulin Resistance

Overview

This investigation is being carried out to learn more about research findings from a study that was completed last year. Those findings revealed that within the skeletal muscle cells of individuals with type 2 diabetes, there was often damage to the mitochondria (the muscle cell's power source or the machinery of the muscle cell that produces energy). In individuals with type 2 diabetes, the liver continues to release sugar even when sugar levels are normal; the pancreas is not able to produce and release insulin normally; and the muscle and fat cells no longer respond as effectively to insulin. These defects lead to an abnormal rise of sugar in the blood. In this study, we want both to look more closely at the mitochondria and see if there is potential for improving mitochondrial functioning (improving the machinery of the muscle cell that produces energy) and reversing mitochondrial damage through a weight loss or a combined exercise/weight loss program. The program you get assigned to will be determined by a process called randomization (like a flip of a coin).

Recent research from our laboratory has detected novel findings concerning damage to mitochondria within skeletal muscle in type 2 diabetes (type 2 DM), damage that is evident morphologically and by functional criteria. In this project, we propose, firstly, to more fully test this hypothesis of an impaired bio-energetic capacity, and to begin to examine the pathogenesis of damage to mitochondria in type 2 DM. We are also interested in assessing the potential for reversing damage, and improving functional capacity of mitochondria through a weight loss or a combined exercise and weight loss intervention. The first specific aim is to measure the functional capacity of mitochondria in human skeletal muscle in type 2 DM and in those at apparent risk for type 2 DM (obese, sedentary, non-diabetic adults with the Metabolic Syndrome and/or impaired glucose tolerance). The second specific aim is to examine the morphology of mitochondria in human skeletal muscle in type 2 DM and in those at apparent risk for type 2 DM. The third specific aim is to examine the pathogenesis of mitochondrial damage in type 2 DM and in those at apparent risk for type 2 DM. The fourth specific aim is to assess whether exercise and diet can improve mitochondrial function and morphology in type 2 DM and in those at apparent risk for type 2 DM.