Adaptation of Insulin Clearance to Metabolic Demand Is a Key Determinant of Glucose Tolerance
Adaptation of Insulin Clearance to Metabolic Demand Is a Key Determinant of Glucose Tolerance
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DOI：
10.2337/db19-1152
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发表时间：
2021-02-01
期刊：
影响因子：
7.7
通讯作者：
DeFronzo, Ralph A.
中科院分区：
文献类型：
--
作者：
Gastaldelli, Amalia;Abdul Ghani, Muhammad;DeFronzo, Ralph A.
随着胰岛素抵抗（IR）的发展，血浆胰岛素反应代偿性增加，以抵消胰岛素作用的缺陷，维持正常的葡萄糖耐量。胰岛素反应是胰岛素分泌和胰岛素代谢清除率（MCRI）两个因素共同作用的结果。受试者（糖耐量正常[NGT] 104例，糖耐量受损[IGT] 57例，2型糖尿病[T2DM] 207例）分为非肥胖组和肥胖组，接受正糖胰岛素钳夹（40 mU/m）(2)。min)和口服葡萄糖耐量试验（OGTT） （75 g），分别于隔天进行。在使用[3-H-3]葡萄糖和OGTT进行胰岛素钳夹期间计算MCRI，并与IR相关：外周（胰岛素钳夹期间的葡萄糖摄取），肝脏（基础内源性葡萄糖生成x空腹血浆胰岛素[FPI]）和脂肪细胞（空腹游离脂肪酸x FPI）。胰岛素钳夹期间肥胖NGT患者的MCRI比非肥胖NGT患者降低（0.60 +/- 0.03 vs 0.73 +/- 0.02 L/min）。m(2), P < 0.001)，非肥胖型IGT (0.62 +/- 0.02, P < 0.004)，非肥胖型T2DM （0.68 +/- 0.02, P < 0.03）。胰岛素钳夹期间的MCRI与IR呈显著负相关（r = -0.52, P < 0.0001）。在OGTT期间，NGT和IGT受试者的MCRI在15-30分钟内被抑制并保持抑制状态。相比之下，T2DM的抑制最小。总之，肥胖受试者IR的发展与MCRI的下降有关，这代表了维持正常葡萄糖耐量的代偿反应，但在T2DM患者中受损。
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 (MCRI). 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(2) . min) and an oral glucose tolerance test (OGTT) (75 g) on separate days. MCRI was calculated during the insulin-clamp performed with [3-H-3]glucose and the OGTT and related to IR: peripheral (glucose uptake during the insulin clamp), hepatic (basal endogenous glucose production x fasting plasma insulin [FPI]), and adipocyte (fasting free fatty acid x FPI). MCRI during the insulin clamp was reduced in obese versus nonobese NGT (0.60 +/- 0.03 vs. 0.73 +/- 0.02 L/min . m(2), P < 0.001), in nonobese IGT (0.62 +/- 0.02, P < 0.004), and in nonobese T2DM (0.68 +/- 0.02, P < 0.03). The MCRI during the insulin clamp was strongly and inversely correlated with IR (r = -0.52, P < 0.0001). During the OGTT, the MCRI 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 MCRI that represents a compensatory response to maintain normal glucose tolerance but is impaired in individuals with T2DM.