Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR), Pisa, Italy
University of Texas Health Science Center, San Antonio, TX.
Diabetes. 2021 Feb;70(2):377-385. doi: 10.2337/db19-1152. Epub 2020 Oct 19.
With the development of insulin resistance (IR), there is a compensatory increase in the plasma insulin response to offset the defect in insulin action to maintain normal glucose tolerance. The insulin response is the result of two factors: insulin secretion and metabolic clearance rate of insulin (MCR). Subjects (104 with normal glucose tolerance [NGT], 57 with impaired glucose tolerance [IGT], and 207 with type 2 diabetes mellitus [T2DM]), divided in nonobese and obese groups, received a euglycemic insulin-clamp (40 mU/m ⋅ min) and an oral glucose tolerance test (OGTT) (75 g) on separate days. MCR was calculated during the insulin-clamp performed with [3-H]glucose and the OGTT and related to IR: peripheral (glucose uptake during the insulin clamp), hepatic (basal endogenous glucose production × fasting plasma insulin [FPI]), and adipocyte (fasting free fatty acid × FPI). MCR during the insulin clamp was reduced in obese versus nonobese NGT (0.60 ± 0.03 vs. 0.73 ± 0.02 L/min ⋅ m, < 0.001), in nonobese IGT (0.62 ± 0.02, < 0.004), and in nonobese T2DM (0.68 ± 0.02, < 0.03). The MCR during the insulin clamp was strongly and inversely correlated with IR ( = -0.52, < 0.0001). During the OGTT, the MCR was suppressed within 15-30 min in NGT and IGT subjects and remained suppressed. In contrast, suppression was minimal in T2DM. In conclusion, the development of IR in obese subjects is associated with a decline in MCR that represents a compensatory response to maintain normal glucose tolerance but is impaired in individuals with T2DM.
随着胰岛素抵抗 (IR) 的发展，血浆胰岛素反应会代偿性增加，以抵消胰岛素作用的缺陷，从而维持正常的葡萄糖耐量。胰岛素反应是两个因素的结果：胰岛素分泌和胰岛素代谢清除率 (MCR)。将受试者（104 例糖耐量正常 [NGT]、57 例糖耐量受损 [IGT] 和 207 例 2 型糖尿病 [T2DM]）分为非肥胖和肥胖两组，分别在不同天进行正常血糖胰岛素钳夹（40 mU/m ⋅ min）和口服葡萄糖耐量试验（OGTT）（75 g）。在胰岛素钳夹期间用 [3-H] 葡萄糖和 OGTT 计算 MCR，并与 IR 相关：外周（胰岛素钳夹期间的葡萄糖摄取）、肝（基础内源性葡萄糖生成 × 空腹血浆胰岛素 [FPI]）和脂肪细胞（空腹游离脂肪酸 × FPI）。与非肥胖 NGT 相比，肥胖者的胰岛素钳夹期间 MCR 降低（0.60 ± 0.03 对 0.73 ± 0.02 L/min ⋅ m， < 0.001），非肥胖 IGT 时降低（0.62 ± 0.02， < 0.004），非肥胖 T2DM 时降低（0.68 ± 0.02， < 0.03）。胰岛素钳夹期间的 MCR 与 IR 呈强烈负相关（ = -0.52，< 0.0001）。在 OGTT 期间，NGT 和 IGT 受试者的 MCR 在 15-30 分钟内被抑制，并保持抑制状态。相比之下，T2DM 患者的抑制作用最小。总之，肥胖者的 IR 发展与 MCR 的下降有关，这代表了维持正常葡萄糖耐量的代偿性反应，但在 T2DM 患者中受损。
