5.糖尿病和痴呆症资料.ppt

* * * * Figure 1 Suggested pathogenesis of cognitive decline in DM2 Insulin resistance and risk factors related to the metabolic syndrome lead to DM2. The adverse effects of the metabolic syndrome and DM2 on the brain are mediated through ischaemic cerebrovascular disease, in concert with other factors from the metabolic syndrome. Hyperglycaemia plays an additional role through ‘toxic’ effects on brain tissue and the development of cerebral microangiopathy. Alterations in insulin metabolism can also directly affect the brain, through involvement in synaptic plasticity and amyloid and tau metabolism. Ischaemic cerebrovascular disease plays a modulating role in these latter processes. * Adjusted relative risk for all dementia in older diabetic adultscompared with non-diabetics in prospective population-based studies. * Adjusted relative risk for Alzheimer’s disease in older diabetic adults compared with non-diabetics in prospective population-based studies. * Adjusted relative risk for vascular dementia in older diabetic adults compared with non-diabetics in prospective population-based studies. * * (上图) Percent CSF A42 increase following insulin infusion relative to saline infusion was age-dependent, with older adults showing larger increases(p .01). (下图）Insulin-induced A42 changes were negatively correlated with insulin-induced memory facilitation for older (age 70 years) adults (r =?.95, p .01). Taken from Watson et al. * * PPARα－过氧化物酶体增殖物激活受体α PPARγ－过氧化物酶体增殖物激活受体γ 过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor, PPAR)是调节目标基因表达的核内受体转录因子超家族成员， 1990 年Issemann 等首先发现了这种能被一类脂肪酸样化合物过氧化物酶体增殖剂(peroxisome proliferators, PP) 激活, 而被命名为PP 激活受体( peroxisome proliferator activated receptor, PPAR)。根据结构的不同，PPAR可分为α、β(或δ)和γ三种类型，其中PPARγ主要表达于脂肪组织及免疫系统，与脂肪细胞分化、机体免疫及胰岛素抵抗关系密切，是胰岛素增敏剂噻唑烷二酮类药物(troglitazone, TZDs)作用的靶分子，成为近年来研究热点 PPAR-Regulated Inflammatory Markers PPARa and PPARg have a positive effect on numerous inflammatory markers that have been associated with athe