Insulin metabolism in Alzheimer's disease differs according to apolipoprotein E genotype and gender
Insulin metabolism in Alzheimer's disease differs according to apolipoprotein E genotype and gender
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DOI：
10.1159/000054469
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发表时间：
1999-08-01
影响因子：
4.1
通讯作者：
Grimwood, K
中科院分区：
文献类型：
--
作者：
Craft, S;Asthana, S;Grimwood, K
在不具有载脂蛋白 E (APOE)ε E4 等位基因的阿尔茨海默病 (AD) 患者中，观察到较高的空腹血浆胰岛素水平和较低的脑脊液与血浆胰岛素比率，表明存在胰岛素抵抗。我们使用胰岛素介导的葡萄糖处理的敏感测量方法，研究了 AD 患者中 APOE 和性别与外周胰岛素作用和高胰岛素记忆促进的关系。参与者包括 32 名 AD 患者（9 名不带 epsilon 4 等位基因，23 名带 epsilon 4 等位基因）和 25 名年龄匹配的健康成年人（16 名不带 epsilon 4 等位基因，9 名带 epsilon 4 等位基因）。没有ε 4等位基因的AD受试者比具有ε 4等位基因的AD患者（p < 0.03）或没有ε 4等位基因的正常成人（p < 0.02）显着降低胰岛素介导的葡萄糖处理率。女性 AD 受试者的胰岛素介导的葡萄糖处理率低于男性 AD 受试者 (p < 0.02)。 APOE 组和性别之间没有观察到显着的相互作用，表明这些影响是独立的。没有ε 4等位基因的AD受试者在高胰岛素血症条件下也表现出显着的记忆促进作用(p < 0.04)，而AD-ε 4组则没有。同样在高胰岛素血症条件下，不带 epsilon 4 等位基因的 AD 患者的胰岛素水平低于带 epsilon 4 等位基因的患者 (p < 0.02)，尽管胰岛素输注率和体重相似，但 AD 女性患者的胰岛素水平低于 AD 男性 (p < 0.004)。对于正常受试者，在这两种情况下均未观察到性别或基因型影响。这些结果提供了ε 4 和非ε 4 AD 之间胰岛素介导的能量代谢差异的体内证据，并表明胰岛素作用缺陷对于没有ε 4 等位基因的患者可能具有特殊的病理生理学意义。
Higher fasting 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 E4 allele. We examined the relationship of APOE and gender to peripheral insulin action and hyperinsulinemic memory facilitation in patients with AD using a sensitive measure of insulin-mediated glucose disposal. Participants were 32 patients with AD (9 without an epsilon 4 allele, 23 with an epsilon 4 allele) and 25 healthy age-matched adults (16 without an epsilon 4 allele, 9 with an epsilon 4 allele). AD subjects without an epsilon 4 allele had significantly lower insulin-mediated glucose disposal rates than AD patients with an epsilon 4 allele (p < 0.03), or than normal adults without an epsilon 4 allele (p < 0.02). Female AD subjects showed lower insulin-mediated glucose disposal rates than did male AD subjects (p < 0.02). No significant interaction was observed between APOE group and gender, suggesting that these effects are independent. AD subjects without an epsilon 4 allele also showed significant memory facilitation in the hyperinsulinemic condition (p < 0.04), whereas the AD-epsilon 4 group did not. Also in the hyperinsulinemic condition, AD patients without an epsilon 4 allele had lower insulin levels than patients with an epsilon 4 allele (p < 0.02), and women with AD had lower insulin levels than did men with AD despite similar insulin infusion rates and body mass (p < 0.004). No gender or genotype effects were observed in either condition for normal subjects. These results provide in vivo evidence of differences in insulin-mediated energy metabolism between epsilon 4 and non-epsilon 4 AD, and suggest that defective insulin action may be of particular pathophysiologic significance for patients without an epsilon-4 allele.