Dept. of Psychology, University at Albany, Albany, NY 12222, USA.
Neurobiol Learn Mem. 2010 May;93(4):546-53. doi: 10.1016/j.nlm.2010.02.002. Epub 2010 Feb 20.
Insulin regulates glucose uptake and storage in peripheral tissues, and has been shown to act within the hypothalamus to acutely regulate food intake and metabolism. The machinery for transduction of insulin signaling is also present in other brain areas, particularly in the hippocampus, but a physiological role for brain insulin outside the hypothalamus has not been established. Recent studies suggest that insulin may be able to modulate cognitive functions including memory. Here we report that local delivery of insulin to the rat hippocampus enhances spatial memory, in a PI-3-kinase dependent manner, and that intrahippocampal insulin also increases local glycolytic metabolism. Selective blockade of endogenous intrahippocampal insulin signaling impairs memory performance. Further, a rodent model of type 2 diabetes mellitus produced by a high-fat diet impairs basal cognitive function and attenuates both cognitive and metabolic responses to hippocampal insulin administration. Our data demonstrate that insulin is required for optimal hippocampal memory processing. Insulin resistance within the telencephalon may underlie the cognitive deficits commonly reported to accompany type 2 diabetes.
胰岛素调节外周组织的葡萄糖摄取和储存,并已被证明在下丘脑内发挥作用,以急性调节食物摄入和新陈代谢。胰岛素信号转导的机制也存在于其他脑区,特别是海马体,但脑胰岛素在下丘脑外的生理作用尚未确定。最近的研究表明,胰岛素可能能够调节认知功能,包括记忆。在这里,我们报告说,胰岛素在海马体内的局部递送以 PI-3-激酶依赖性方式增强空间记忆,并且海马内胰岛素也增加局部糖酵解代谢。内源性海马胰岛素信号的选择性阻断会损害记忆表现。此外,高脂肪饮食引起的 2 型糖尿病的啮齿动物模型会损害基础认知功能,并减弱对海马体胰岛素给药的认知和代谢反应。我们的数据表明,胰岛素是海马体记忆处理的最佳条件。端脑中的胰岛素抵抗可能是伴随 2 型糖尿病常见报道的认知缺陷的基础。