The studies in this thesis contribute to the understanding of the role of the brain in insulin sensitivity. We demonstrate that disturbances in circadian rhythm resulting in alterations in SCN... Show moreThe studies in this thesis contribute to the understanding of the role of the brain in insulin sensitivity. We demonstrate that disturbances in circadian rhythm resulting in alterations in SCN output, can contribute to the development of insulin resistance. We also shown that insulin-stimulated glucose uptake by muscle and insulin-stimulated FA uptake by WAT is in part dependent on insulin action in the brain. These effects of circulating insulin on peripheral organs via the brain are abrogated by high-fat diet. These brain-dependent effects of insulin could reflect a similar situation for other hormones, for instance thyroid hormones. Furthermore, we demonstrate that topiramate improves insulin resistance by restoring insulin sensitivity in the brain, suggesting that therapeutical targets in the brain may offer challenging new approaches to treat insulin resistance of peripheral organs in T2DM. Show less
