Aulinger Benedikt A, Vahl Torsten P, Wilson-Pérez Hilary E, Prigeon Ron L, D'Alessio David A
Division of Endocrinology, Diabetes, and Metabolism (B.A.A., T.P.V., H.E.W.-P., D.A.D.), Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267; University of Maryland School of Medicine (R.L.P.), and Baltimore Veterans Affairs Medical Center, Baltimore, Maryland 21201; and Cincinnati Veterans Affairs Medical Center (D.A.D.), Cincinnati, Ohio 45220.
J Clin Endocrinol Metab. 2015 Jun;100(6):2489-96. doi: 10.1210/jc.2014-4009. Epub 2015 Mar 31.
Glucagon-like peptide-1 (GLP-1) is an insulinotropic factor made in the gastrointestinal tract that is essential for normal glucose tolerance. Infusion of GLP-1 increases insulin secretion in both diabetic and nondiabetic humans. However, the degree to which people vary in their β-cell sensitivity to GLP-1 and the factors contributing to this variability have not been reported.
The objective was to measure the sensitivity of insulin secretion to GLP-1 in cohorts of lean and obese subjects across a broad range of insulin sensitivity.
Insulin secretion was measured during clamped hyperglycemia (7.2 mmol/L) and graded GLP-1 infusion in young, healthy subjects, and GLP-1 sensitivity was computed from the insulin secretion rate (ISR) during progressive increases in plasma GLP-1.
All subjects had fasting glucose values <5.2 mm. The obese subjects were insulin resistant compared to the lean group (homeostasis model of assessment 2 for insulin resistance: obese, 2.6 ± 0.5; lean, 0.8 ± 0.1; P < .001). ISR increased linearly in both cohorts with escalating doses of GLP-1, but the slope of ISR in response to GLP-1 was greater in the obese than in the lean subjects (obese, 0.17 ± 0.03 nmol/min/pm; lean, 0.05 ± 0.01 nmol/min/pm; P < .001). There was a significant association of β-cell GLP-1 sensitivity and insulin resistance (r = 0.83; P < .001), and after correction for homeostasis model of assessment 2 for insulin resistance, the slopes of ISR vs GLP-1 concentration did not differ in the two cohorts (obese, 0.08 ± 0.01; lean, 0.08 ± 0.01; P = .98). However, within the entire study group, β-cell GLP-1 sensitivity corrected for insulin resistance varied nearly 10-fold.
Insulin secretion in response to GLP-1 is proportional to insulin resistance in healthy subjects. However, there is considerable variability in the sensitivity of the β-cell to GLP-1 that is independent of insulin sensitivity.
胰高血糖素样肽-1（GLP-1）是一种在胃肠道产生的促胰岛素分泌因子，对正常糖耐量至关重要。输注GLP-1可增加糖尿病患者和非糖尿病患者的胰岛素分泌。然而，人们对GLP-1的β细胞敏感性差异程度以及导致这种差异的因素尚未见报道。
目的是测量不同胰岛素敏感性的瘦人和肥胖受试者队列中胰岛素分泌对GLP-1的敏感性。
在年轻健康受试者钳夹高血糖（7.2 mmol/L）和分级输注GLP-1期间测量胰岛素分泌，并根据血浆GLP-1逐渐升高时的胰岛素分泌率（ISR）计算GLP-1敏感性。
所有受试者空腹血糖值均<5.2 mmol/L。与瘦组相比，肥胖受试者存在胰岛素抵抗（胰岛素抵抗的稳态模型评估2：肥胖者为2.6±0.5；瘦者为0.8±0.1；P<.001）。随着GLP-1剂量增加，两组的ISR均呈线性增加，但肥胖受试者中ISR对GLP-1反应的斜率大于瘦受试者（肥胖者为0.17±0.03 nmol/min/pm；瘦者为0.05±0.01 nmol/min/pm；P<.001）。β细胞GLP-1敏感性与胰岛素抵抗之间存在显著关联（r=0.83；P<.001），在对胰岛素抵抗的稳态模型评估2进行校正后，两组中ISR与GLP-1浓度的斜率无差异（肥胖者为0.08±0.01；瘦者为0.08±0.01；P=.98）。然而，在整个研究组中，校正胰岛素抵抗后的β细胞GLP-1敏感性差异近10倍。
在健康受试者中，对GLP-1的胰岛素分泌与胰岛素抵抗成正比。然而，β细胞对GLP-1的敏感性存在相当大的差异，且与胰岛素敏感性无关。
