Gispen W H, Biessels G J
Dept of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, University Medical Centre Utrecht, PO Box 85060Box 3508AB, Utrecht, The Netherlands.
Trends Neurosci. 2000 Nov;23(11):542-9. doi: 10.1016/s0166-2236(00)01656-8.
Diabetes mellitus is associated with cognitive deficits and an increased risk of dementia, particularly in the elderly. These deficits are paralleled by neurophysiological and structural changes in the brain. In animal models of diabetes, impairments of spatial learning occur in association with distinct changes in hippocampal synaptic plasticity. At the molecular level these impairments might involve changes in glutamate-receptor subtypes, in second-messenger systems and in protein kinases. The multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood, but clearly shares features with brain ageing and the pathogenesis of diabetic neuropathy. It involves both metabolic and vascular changes, related to chronic hyperglycaemia, but probably also defects in insulin action in the brain. Treatment with insulin might therefore not only correct hyperglycaemia, but could also directly affect the brain.
糖尿病与认知缺陷以及痴呆风险增加有关,尤其是在老年人中。这些缺陷与大脑的神经生理和结构变化同时出现。在糖尿病动物模型中,空间学习障碍与海马突触可塑性的明显变化相关。在分子水平上,这些障碍可能涉及谷氨酸受体亚型、第二信使系统和蛋白激酶的变化。糖尿病性脑病的多因素发病机制尚未完全明了,但显然与脑老化及糖尿病性神经病变的发病机制有共同特征。它涉及与慢性高血糖相关的代谢和血管变化,但可能还包括大脑中胰岛素作用的缺陷。因此,胰岛素治疗可能不仅能纠正高血糖,还可能直接影响大脑。