Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany.
Diabetes Res Clin Pract. 2011 Aug;93 Suppl 1:S47-51. doi: 10.1016/S0168-8227(11)70013-4.
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.
大脑是一个对胰岛素敏感的器官，胰岛素信号对于调节摄食行为、体重和认知过程非常重要。外周组织的胰岛素抵抗是 2 型糖尿病（T2DM）发展的标志，但大脑中的胰岛素抵抗是相对较新的发现。人类研究表明，肥胖、年龄和遗传背景等环境因素会影响中枢胰岛素敏感性。根据胰岛素在大脑中的生理作用，这条信号链的紊乱会导致认知功能障碍和进食行为恶化，这可能在肥胖和 T2DM 的发病机制中起作用。因此，人们首次尝试不仅治疗外周组织，还治疗中枢神经系统的胰岛素抵抗：通过鼻腔内给予胰岛素或通过具有特定脑内作用的商业胰岛素进行治疗，可以部分克服大脑中的胰岛素抵抗，这是由于它们的药代动力学特性。尽管近年来人们对人类大脑中胰岛素功能的理解取得了进展，但要更深入地了解中枢胰岛素功能的机制，并确定克服胰岛素抵抗的进一步策略，仍将是未来研究的主要目标。
