Reduced Insulin Clearance and Insulin-Degrading Enzyme Activity Contribute to Hyperinsulinemia in African Americans
Reduced Insulin Clearance and Insulin-Degrading Enzyme Activity Contribute to Hyperinsulinemia in African Americans
复制标题
DOI：
10.1210/clinem/dgaa070
复制
发表时间：
2020-04-01
影响因子：
5.8
通讯作者：
Muniyappa, Ranganath
中科院分区：
文献类型：
--
作者：
Fosam, Andin;Sikder, Shanaz;Muniyappa, Ranganath
背景：与非西班牙裔白人（NHW）相比，非洲裔美国人（AA）患2型糖尿病的风险更高。β细胞葡萄糖敏感性（beta-GS）和胰岛素清除率在AA成人高胰岛素血症中的因果作用尚不清楚。目的：采用横断面研究设计，我们比较了混合餐试验（MMT）后非糖尿病AA（n = 36）和NHW（n = 47）的β细胞功能和胰岛素清除率。胰岛素分泌率，葡萄糖敏感性，速率敏感性，胰岛素敏感性在MMT的数学模型。胰岛素降解酶（IDE）和癌胚抗原相关细胞粘附分子-1（CEACAM 1）的水平，在胰岛素清除的关键球员，测定（酶联免疫吸附试验）肝细胞溶质组分从年龄，性别和体重指数匹配的AA和NHW尸体供体（n = 10）。AA有显着较高的空腹和平均餐后血浆胰岛素水平。然而，两组之间的空腹ISR、总胰岛素输出量和MMT期间的胰岛素敏感性没有差异。AAs的β-GS和速率敏感性较高。AA组空腹和餐时血浆胰岛素清除率较低。AA和NHW中IDE和CEACAM-1的肝脏水平相似。肝脏IDE活性显着降低AAS.Conclusions：在这项研究中，较低的胰岛素清除率有助于较高的血浆胰岛素水平在AA。胰岛素清除率降低可通过AA中IDE活性水平降低来解释。需要进行进一步的确证性研究，以研究由于IDE活性水平降低而导致AA中胰岛素清除率降低。
Background: African Americans (AAs) are at a higher risk for developing type 2 diabetes compared with non-Hispanic whites (NHWs). The causal role of beta-cell glucose sensitivity (beta-GS) and insulin clearance in hyperinsulinemia in AA adults is unclear.Objective: Using a cross-sectional study design, we compared beta-cell function and insulin clearance in nondiabetic AAs (n = 36) and NHWs (n = 47) after a mixed meal test (MMT).Methods: Insulin secretion rate, glucose sensitivity, rate sensitivity, and insulin sensitivity during MMT were derived from a mathematical model. Levels of insulin-degrading enzyme (IDE) and carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1), key players in insulin clearance, were measured (by enzyme-linked immunosorbent assay) in hepatic cytosolic fractions from age-, sex-, and body mass index-matched AA and NHW cadaveric donors (n = 10).Results: Fasting and mean postprandial plasma glucose levels were similar in both ethnic groups. AAs had significantly higher fasting and mean postprandial plasma insulin levels. However, fasting ISR, total insulin output, and insulin sensitivity during MMT were not different between the groups. beta-GS and rate sensitivity were higher in AAs. Fasting and meal plasma insulin clearance were lower in AAs. Hepatic levels of IDE and CEACAM-1 were similar in AAs and NHWs. Hepatic IDE activity was significantly lower in AAs.Conclusions: In this study, lower insulin clearance contributes to higher plasma insulin levels in AAs. Reduced insulin clearance may be explained by lower IDE activity levels in AAs. Further confirmatory studies are needed to investigate diminished insulin clearance in AAs as a result of lower IDE activity levels.