Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
Front Endocrinol (Lausanne). 2023 Jul 19;14:1195658. doi: 10.3389/fendo.2023.1195658. eCollection 2023.
Previous experimental studies have shown that mice overexpressing amyloid precursor protein, in which β-amyloid (Aβ) is overproduced, exhibit peripheral insulin resistance, pancreatic impairment, and hyperglycemia. We aimed to explore the effects of Aβ on insulin action and insulin secretion and the association of plasma Aβ with prediabetes in human.
We examined the effects of Aβ40 and Aβ42 on insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and insulin secretion in INS-1 cells. Furthermore, we conducted a case-control study (N = 1142) and a nested case-control study (N = 300) within the prospective Tongji-Ezhou cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) for prediabetes were estimated by using conditional logistic regression analyses.
In the studies, Aβ40 and Aβ42 dose-dependently attenuated insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and basal and glucose-stimulated insulin secretion in INS-1 cells. In the case-control study, plasma Aβ40 (adjusted OR: 2.00; 95% CI: 1.34, 3.01) and Aβ42 (adjusted OR: 1.94; 95% CI: 1.33, 2.83) were positively associated with prediabetes risk when comparing the extreme quartiles. In the nested case-control study, compared to the lowest quartile, the highest quartile of plasma Aβ40 and Aβ42 were associated with 3.51-fold (95% CI: 1.61, 7.62) and 2.75-fold (95% CI: 1.21, 6.22) greater odds of prediabetes, respectively.
Elevated plasma Aβ40 and Aβ42 levels were associated with increased risk of prediabetes in human subjects, which may be through impairing insulin sensitivity in hepatocytes and myotubes and insulin secretion in pancreatic β-cells.
先前的实验研究表明，过度表达淀粉样前体蛋白的小鼠，其中β-淀粉样蛋白（Aβ）过度产生，表现出外周胰岛素抵抗、胰腺损伤和高血糖。我们旨在探讨 Aβ 对胰岛素作用和胰岛素分泌的影响，以及人血浆 Aβ 与糖尿病前期的关系。
我们研究了 Aβ40 和 Aβ42 对 HepG2 细胞中胰岛素抑制的葡萄糖生成、C2C12 肌管中胰岛素促进的葡萄糖摄取以及 INS-1 细胞中胰岛素分泌的影响。此外，我们在前瞻性同济-鄂州队列中进行了病例对照研究（N=1142）和巢式病例对照研究（N=300）。采用条件逻辑回归分析估计糖尿病前期的比值比（OR）和 95%置信区间（CI）。
在这些研究中，Aβ40 和 Aβ42 呈剂量依赖性地减弱了 HepG2 细胞中胰岛素抑制的葡萄糖生成、C2C12 肌管中胰岛素促进的葡萄糖摄取以及 INS-1 细胞中的基础和葡萄糖刺激的胰岛素分泌。在病例对照研究中，与极端四分位数相比，血浆 Aβ40（调整后的 OR：2.00；95%CI：1.34，3.01）和 Aβ42（调整后的 OR：1.94；95%CI：1.33，2.83）与糖尿病前期风险呈正相关。在巢式病例对照研究中，与最低四分位数相比，血浆 Aβ40 和 Aβ42 的最高四分位数与糖尿病前期的比值分别为 3.51 倍（95%CI：1.61，7.62）和 2.75 倍（95%CI：1.21，6.22）。
血浆 Aβ40 和 Aβ42 水平升高与人类糖尿病前期风险增加相关，这可能是通过损害肝细胞和肌管中的胰岛素敏感性以及胰腺β细胞中的胰岛素分泌。
