Impact of Obesity on Postprandial Triglyceride Contribution to Glucose Homeostasis, Assessed with a Semimechanistic Model.

Autor: Leohr J; Department of Pharmacokinetics/Pharmacodynamics, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana, USA., Kjellsson MC; Pharmacometrics Research Group, Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2022 Jul; Vol. 112 (1), pp. 112-124. Date of Electronic Publication: 2022 May 15.
DOI: 10.1002/cpt.2604
Abstrakt: 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.
(© 2022 Eli Lilly and Co. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC On behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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