肠促胰岛素
内科学
内分泌学
葡萄糖稳态
抵抗素
能量稳态
受体
胃抑制多肽
胰岛素抵抗
胰岛素
生物
化学
2型糖尿病
胰高血糖素
糖尿病
医学
脂肪因子
作者
Tanya Hansotia,Adriano Maida,Grace Flock,Yoshio Yamada,Katsushi Tsukiyama,Yutaka Seino,Daniel J. Drucker
摘要
The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) control glucose homeostasis through well-defined actions on the islet beta cell via stimulation of insulin secretion and preservation and expansion of beta cell mass. We examined the importance of endogenous incretin receptors for control of glucose homeostasis through analysis of Glp1r(-/-), Gipr(-/-), and double incretin receptor knockout (DIRKO) mice fed a high-fat (HF) diet. DIRKO mice failed to upregulate levels of plasma insulin, pancreatic insulin mRNA transcripts, and insulin content following several months of HF feeding. Both single incretin receptor knockout and DIRKO mice exhibited resistance to diet-induced obesity, preservation of insulin sensitivity, and increased energy expenditure associated with increased locomotor activity. Moreover, plasma levels of plasminogen activator inhibitor-1 and resistin failed to increase significantly in DIRKO mice after HF feeding, and the GIP receptor agonist [D-Ala(2)]GIP, but not the GLP-1 receptor agonist exendin-4, increased the levels of plasma resistin in studies of both acute and chronic administration. These findings extend our understanding of how endogenous incretin circuits regulate glucose homeostasis independent of the beta cell via control of adipokine secretion and energy expenditure.
科研通智能强力驱动
Strongly Powered by AbleSci AI