Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus
Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus
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DOI：
10.1210/jc.2002-021873
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发表时间：
2003-06-01
影响因子：
5.8
通讯作者：
Holst, JJ
中科院分区：
文献类型：
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作者：
Vilsboll, T;Krarup, T;Holst, JJ
胰高血糖素样肽-1(GLP-1)和葡萄糖依赖的促胰岛素多肽(GIP)是在进食后分泌的胰岛素激素，从而促进餐后胰岛素的分泌。因此，胰岛素反应减弱可能是糖尿病患者胰岛素反应受损的原因之一。本研究的目的是调查肥胖和1型和2型糖尿病患者的胰岛素分泌及其对饮食刺激的依赖程度。本文测定了8例1型糖尿病患者、8例消瘦健康者、8例肥胖2型糖尿病患者和8例肥胖者的两次进餐试验(260千卡和520千卡)的血浆胰岛素激素(总的、反映分泌的和完整的、反映潜在作用的)浓度。在糖尿病患者和健康受试者中，摄取两餐后GLP-1和GIP浓度均显著升高。与小餐相比，大餐后所有组的胰岛素反应均显著升高，相应地C肽反应也较高。与健康受试者相比，1型和2型糖尿病患者的GIP反应均正常，而与匹配的肥胖健康受试者相比，2型糖尿病患者的GLP-1反应降低。在1型糖尿病患者中，GLP-1的升高反应是正常的。与瘦的健康受试者相比，肥胖者的空腹GIP浓度升高和餐后GIP反应早期增强，而GLP-1反应在两组中相同。在2型糖尿病患者(29%，P=0.19)和肥胖健康受试者(22%，P=0.04)中，β细胞对葡萄糖的敏感性(用胰岛素分泌率与血糖浓度的斜率进行评估)在大餐期间倾向于增加，这可能反映了胰岛素反应的增加。我们的结论是：1)GLP-1分泌减少可能是2型糖尿病患者胰岛素分泌受损的原因之一，而GIP和GLP-1分泌在1型糖尿病患者中是正常的；2)与小餐相比，肥胖健康受试者，以及2型糖尿病患者，通过多吃一餐来调节β细胞对葡萄糖的敏感性是可能的。
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones secreted in response to meal ingestion, thereby enhancing postprandial insulin secretion. Therefore, an attenuated incretin response could contribute to the impaired insulin responses in patients with diabetes mellitus. The aim of the present investigation was to investigate incretin secretion, in obesity and type 1 and type 2 diabetes mellitus, and its dependence on the magnitude of the meal stimulus. Plasma concentrations of incretin hormones (total, reflecting secretion and intact, reflecting potential action) were measured during two meal tests (260 kcal and 520 kcal) in eight type 1 diabetic patients, eight lean healthy subjects, eight obese type 2 diabetic patients, and eight obese healthy subjects. Both in diabetic patients and in healthy subjects, significant increases in GLP-1 and GIP concentrations were seen after ingestion of both meals. The incretin responses were significantly higher in all groups after the large meal, compared with the small meal, with correspondingly higher C-peptide responses. Both type 1 and type 2 diabetic patients had normal GIP responses, compared with healthy subjects, whereas decreased GLP-1 responses were seen in type 2 diabetic patients, compared with matched obese healthy subjects. Incremental GLP-1 responses were normal in type 1 diabetic patients. Increased fasting concentrations of GIP and an early enhanced postprandial GIP response were seen in obese, compared with lean healthy subjects, whereas GLP-1 responses were the same in the two groups. beta-cell sensitivity to glucose, evaluated as the slope of insulin secretion rates vs. plasma glucose concentration, tended to increase in both type 2 diabetic patients (29%, P=0.19) and obese healthy subjects (22% P=0.04) during the large meal, compared with the small meal, perhaps reflecting the increased incretin response. We conclude: 1) that a decreased GLP-1 secretion may contribute to impaired insulin secretion in type 2 diabetes mellitus, whereas GIP and GLP-1 secretion is normal in type 1 diabetic patients; and 2) that it is possible to modulate the beta-cell sensitivity to glucose in obese healthy subjects, and possibly also in type 2 diabetic patients, by giving them a large meal, compared with a small meal.