The brain is an insulin sensitive organ and insulin signaling is important to regulate feeding behavior, body weight, and cognitive processes. Insulin resistance in peripheral tissues is a hallmark in the development of type 2 diabetes mellitus (T2DM), yet the finding of insulin resistance in the brain is relatively novel. Studies in humans revealed that environmental factors like obesity, age, and the genetic background have an impact on central insulin sensitivity. According to the physiological effects of insulin in the brain, disturbances of this signaling chain lead to an impairment of cognitive functions and a deterioration of eating behavior with a potential role in the pathogenesis of obesity and T2DM. First attempts to treat insulin resistance not only in peripheral tissues but also in the CNS have therefore come on its way: Cerebral insulin resistance can at least partially be overcome by intranasal treatment with insulin or by commercial insulins that exhibit specific effects in the brain due to their pharmacokinetic properties. Despite the advances towards a better understanding of insulin function in the human brain in the last years, achieving a more profound knowledge of mechanisms behind central insulin function and identifying further strategies to overcome insulin resistance must be a main goal of future research.
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