Department of Pharmacokinetics/Pharmacodynamics, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, USA.
Pharmacometrics Research Group, Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Clin Pharmacol Ther. 2022 Jul;112(1):112-124. doi: 10.1002/cpt.2604. Epub 2022 May 15.
The integrated glucose-insulin model is a semimechanistic model describing glucose and insulin after a glucose challenge. Similarly, a semiphysiologic model of the postprandial triglyceride (TG) response in chylomicrons and VLDL-V6 was recently published. We have developed the triglyceride-insulin-glucose-GLP-1 (TIGG) model by integrating these models and active GLP-1. The aim was to characterize, using the TIGG model, the postprandial response over 13 hours following a high-fat meal in 3 study populations based on body mass index categories: lean, obese, and very obese. Differential glucose and lipid regulation were observed between the lean population and obese or very obese populations. A population comparison revealed further that fasting glucose and insulin were elevated in obese and very obese when compared with lean; and euglycemia was achieved at different times postmeal between the obese and very obese populations. Postprandial insulin was incrementally elevated in the obese and very obese populations compared with lean. Postprandial chylomicrons TGs were similar across populations, whereas the postprandial TGs in VLDL-V6 were increased in the obese and very obese populations compared with lean. Postprandial active GLP-1 was diminished in the very obese population compared with lean or obese. The TIGG model described the response following a high-fat meal in individuals who are lean, obese, and very obese and provided insight into the possible regulation of glucose homeostasis in the extended period after the meal by utilizing lipids. The TIGG-model is the first model to integrate glucose and insulin regulation, incretin effect, and postprandial TGs response in chylomicrons and VLDL-V6.
整合的葡萄糖-胰岛素模型是一种半机理模型,描述了葡萄糖和胰岛素在葡萄糖冲击后的情况。同样,最近也发表了一种描述乳糜微粒和 VLDL-V6 餐后甘油三酯 (TG) 反应的半生理模型。我们通过整合这些模型和活性 GLP-1 开发了甘油三酯-胰岛素-葡萄糖-GLP-1 (TIGG) 模型。目的是使用 TIGG 模型来描述在三个基于体重指数类别的研究人群中,高脂肪餐后 13 小时内的餐后反应:瘦、胖和非常胖。观察到瘦人群与肥胖或非常肥胖人群之间存在不同的葡萄糖和脂质调节。人群比较进一步表明,与瘦人群相比,肥胖和非常肥胖人群的空腹血糖和胰岛素升高;肥胖和非常肥胖人群在餐后达到血糖正常的时间不同。与瘦人群相比,肥胖和非常肥胖人群的餐后胰岛素逐渐升高。餐后乳糜微粒 TG 在各人群中相似,而 VLDL-V6 中的餐后 TG 在肥胖和非常肥胖人群中增加。与瘦或肥胖人群相比,非常肥胖人群的餐后活性 GLP-1 减少。TIGG 模型描述了瘦、胖和非常胖个体在高脂肪餐后的反应,并通过利用脂质,深入了解了餐后延长时间内葡萄糖稳态的可能调节。TIGG 模型是第一个整合葡萄糖和胰岛素调节、肠促胰岛素效应以及乳糜微粒和 VLDL-V6 餐后 TG 反应的模型。