Alsalim Wathik, Omar Bilal, Pacini Giovanni, Bizzotto Roberto, Mari Andrea, Ahrén Bo
Department of Clinical Sciences (W.A., B.O., B.A.), Lund University, 221 84 Lund, Sweden; and Metabolic Unit (G.P., R.B., A.M.), Institute of Biomedical Engineering, Consiglio Nazionale delle Ricerche, 35127 Padova, Italy.
J Clin Endocrinol Metab. 2015 Feb;100(2):561-8. doi: 10.1210/jc.2014-2865. Epub 2014 Nov 6.
Postprandial glucose homeostasis is regulated through the secretion of glucagon-like peptide 1 (GLP-1) through the stimulation of insulin secretion and inhibition of glucagon secretion. However, how these processes dynamically adapt to demands created by caloric challenges achieved during daily life is not known.
The objective of the study was to explore the adaptation of incretin and islet hormones after mixed meals of increasing size in healthy subjects.
Twenty-four healthy lean subjects ingested a standard breakfast after an overnight fast followed, after 4 hours, by a lunch of a different size (511, 743, and 1034 kcal) but with identical nutrient composition together with 1.5 g paracetamol. Glucose, insulin, C-peptide, glucagon, intact GLP-1, and glucose-dependent insulinotropic polypeptide (GIP) and paracetamol were measured after the meals.
Area under the 180-minute curve (AUC) for insulin, C-peptide, glucagon, GLP-1, and GIP and model-derived β-cell function and paracetamol appearance were calculated.
Glucose profiles were similar after the two larger meals, whereas after the smaller meal, there was a postpeak reduction below baseline to a nadir of 3.8 ± 0.1 mmol/L after 75 minutes (P < .001). The AUC for GLP-1, GIP, insulin, and C-peptide were significantly higher by increasing the caloric load as was β-cell sensitivity to glucose. In contrast, the AUC glucagon was the same for all three meals, although there was an increase in glucagon after the postpeak glucose reduction in the smaller meal. The 0- to 20-minute paracetamol appearance was increased by increasing meal size.
Mixed lunch meals of increasing size elicit a caloric-dependent insulin response due to increased β-cell secretion achieved by increased GIP and GLP-1 levels. The adaptation at larger meals results in identical glucose excursions, whereas after a lower caloric lunch, the insulin response is high, resulting in a postpeak suppression of glucose below baseline.
餐后血糖稳态通过胰高血糖素样肽-1（GLP-1）的分泌来调节，其可刺激胰岛素分泌并抑制胰高血糖素分泌。然而，这些过程如何动态适应日常生活中热量挑战所产生的需求尚不清楚。
本研究的目的是探讨健康受试者在进食量逐渐增加的混合餐后肠促胰岛素和胰岛激素的适应性变化。
24名健康瘦受试者在禁食过夜后摄入标准早餐，4小时后，再摄入不同热量（511、743和1034千卡）但营养成分相同的午餐，并同时服用1.5克对乙酰氨基酚。餐后测量血糖、胰岛素、C肽、胰高血糖素、完整的GLP-1、葡萄糖依赖性促胰岛素多肽（GIP）和对乙酰氨基酚。
计算胰岛素、C肽、胰高血糖素、GLP-1和GIP的180分钟曲线下面积（AUC）以及模型推导的β细胞功能和对乙酰氨基酚的出现情况。
两顿较大餐食后的血糖曲线相似，而较小餐食后，餐后峰值后血糖降至基线以下，75分钟时达到最低点3.8±0.1毫摩尔/升（P<.001）。随着热量负荷增加，GLP-1、GIP、胰岛素和C肽的AUC以及β细胞对葡萄糖的敏感性显著升高。相比之下，尽管较小餐食餐后峰值血糖降低后胰高血糖素有所增加，但三餐的胰高血糖素AUC相同。随着餐量增加，对乙酰氨基酚在0至20分钟的出现量增加。
随着餐量增加，混合午餐会引发热量依赖性胰岛素反应，这是由于GIP和GLP-1水平升高导致β细胞分泌增加所致。较大餐量时的适应性变化导致血糖波动相同，而热量较低的午餐后，胰岛素反应较高，导致餐后峰值血糖抑制至基线以下。
