1Joslin Diabetes Center, Boston, Massachusetts, USA.
Diabetes. 2012 Feb;61(2):301-9. doi: 10.2337/db11-1067.
Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic β-cell dysfunction, the latter possibly caused by a defect in insulin signaling in β-cells. We hypothesized that insulin's effect to potentiate glucose-stimulated insulin secretion (GSIS) would be diminished in insulin-resistant persons. To evaluate the effect of insulin to modulate GSIS in insulin-resistant compared with insulin-sensitive subjects, 10 participants with impaired glucose tolerance (IGT), 11 with T2D, and 8 healthy control subjects were studied on two occasions. The insulin secretory response was assessed by the administration of dextrose for 80 min following a 4-h clamp with either saline infusion (sham) or an isoglycemic-hyperinsulinemic clamp using B28-Asp-insulin (which can be distinguished immunologically from endogenous insulin) that raised insulin concentrations to high physiologic concentrations. Pre-exposure to insulin augmented GSIS in healthy persons. This effect was attenuated in insulin-resistant cohorts, both those with IGT and those with T2D. Insulin potentiates glucose-stimulated insulin secretion in insulin-resistant subjects to a lesser degree than in normal subjects. This is consistent with an effect of insulin to regulate β-cell function in humans in vivo with therapeutic implications.
2 型糖尿病（T2D）的特征是胰岛素抵抗和胰腺β细胞功能障碍，后者可能是由于β细胞中胰岛素信号转导的缺陷引起的。我们假设胰岛素增强葡萄糖刺激的胰岛素分泌（GSIS）的作用在胰岛素抵抗的人中会减弱。为了评估胰岛素对胰岛素抵抗与胰岛素敏感受试者的 GSIS 调节作用，我们在两次研究中对 10 名糖耐量受损（IGT）患者、11 名 T2D 患者和 8 名健康对照者进行了研究。通过给予葡萄糖 80 分钟，在盐水输注（假）或使用 B28-Asp-胰岛素（可从内源性胰岛素免疫上区分）进行 4 小时钳夹后评估胰岛素分泌反应，该胰岛素可将胰岛素浓度升高至生理高浓度。胰岛素的预先暴露增强了健康人的 GSIS。这种作用在胰岛素抵抗组中减弱，无论是 IGT 还是 T2D 患者。胰岛素增强胰岛素抵抗受试者的葡萄糖刺激胰岛素分泌的程度低于正常受试者。这与胰岛素在体内调节β细胞功能的作用一致，具有治疗意义。
