Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype
Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype
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DOI：
10.1111/j.1749-6632.2000.tb06371.x
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Plymate, S
中科院分区：
文献类型：
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作者：
Craft, S;Asthana, S;Plymate, S
在不具有载脂蛋白 E (ApoE)-ε 4 等位基因的阿尔茨海默氏病 (AD) 患者中，观察到较高的持续血浆胰岛素水平和脑脊液与血浆胰岛素比率降低，提示存在胰岛素抵抗，胰岛素还与 β-淀粉样蛋白和淀粉样前体蛋白 (APP) 的加工有关。 在AD患者和不同ApoE基因型的正常成人中，静脉注射胰岛素，同时维持胰岛素介导的葡萄糖处理、记忆和血浆APP的正常血糖，不带ε4等位基因的AD受试者的胰岛素介导的葡萄糖处理率显着低于带ε4等位基因的AD患者（p <0.03）或不带ε4等位基因的正常成人。 等位基因（p < 0.02）。没有 e4 等位基因的 AD 受试者也显示出胰岛素给药显着促进记忆 (p < 0.04)，而 AD-ε 4 组则没有。胰岛素降低了没有 ApoE epsilon 4 等位基因的 AD 患者的 APP 水平，但提高了有 ApoE epsilon H4 等位基因的 AD 患者的 APP 这些结果记录了 AD 中胰岛素代谢中与 ApoE 相关的差异，可能与疾病发病机制有关。
Higher lasting plasma Insulin levels and reduced CSF-to-plasma insulin ratios, suggestive of insulin resistance, have been observed In patients with Alzheimer's disease (AD) who do not possess an apolipoprotein E (ApoE)-epsilon 4 allele, Insulin has also been implicated in processing of beta-amyloid and amyloid precursor protein (APP), We examined the effects of intravenous insulin administration while maintaining euglycemia on insulin-mediated glucose disposal, memory, and plasma APP in patients with AD and normal adults of varying ApoE genotypes, AD subjects without an epsilon 4 allele had significantly lower insulin-mediated glucose disposal rates than did AD patients with an epsilon 4 allele (p < 0.03) or than did normal adults without an epsilon 4 allele (p < 0.02). AD subjects without an e4 allele also showed significant memory facilitation with insulin administration (p < 0.04), whereas the AD-epsilon 4 group did not, Insulin reduced APP levels for AD patients without an ApoE epsilon 4 allele, but raised APP for AD patients with an ApoE epsilon H4 allele These results document ApoE-related differences in insulin metabolism in AD that may relate to disease pathogenesis.