Abnormalities in the Effects of Insulin and Exercise on Glucose- and Lipid Metabolism in Obesity and Type 2 Diabetes

Type 2 diabetes are characterized by insulin resistance in skeletal muscle. Insulin resistance plays a major role for the increased risk of heart disease seen in type 2 diabetes. No specific treatment of insulin resistance is currently available, except from increased physical activity and weight-loss. Insulin resistance is characterized by abnormalities in the use of glucose and fat in the muscle, and is associated with abnormal function and content of mitochondria (the power houses of our cells) as well as increased levels of fat within the muscle. The investigators believe that abnormalities in the use of glucose and fat in muscle cells in response to insulin and exercise can explain why insulin resistance is associated with abnormal function and content of mitochondria and an increased amount of fat in skeletal muscle of patients with type 2 diabetes and individuals with obesity. The major purpose of our project is, therefore, to investigate the effect of insulin in physiological concentrations and the effect of both acute exercise and 8 weeks of high intensity interval exercise-training on 1. insulin sensitivity, body composition, cardiorespiratory fitness and energy metabolism, 2. insulin signaling, mitochondrial dynamics and mitophagy in skeletal muscle 4\) regulators of storage of fat into lipid droplets and their interaction with mitochondria in skeletal muscle 5) acetylation and phosphorylation of enzymes (proteins) in major metabolic and signaling pathways, as well as 6) transcriptional and signalling networks regulating mitochondrial biogenesis and substrate metabolism. The effects of insulin in physiological concentrations and a novel exercise-intervention combining biking and rowing will be studied in a comprehensive study of obese patients with type 2 diabetes compared with weight-matched obese and lean healthy controls. The effects of insulin before and after 8 weeks HIIT on whole-body metabolism will be evaluated by measurement of maximal oxy