内科学
内分泌学
葡萄糖稳态
生物
平衡
垂体前叶
激素
胰岛素
胰岛素抵抗
医学
作者
Shun-Mei Liu,Bruno Ifebi,Fred Johnson Iii,Alison Xu,Jacquelin Ho,Yunlei Yang,Gary J Schwartz,Young-Hwan Jo,Streamson Chua
摘要
Glucose homeostasis can be improved after bariatric surgery that alters bile flow and stimulate gut hormone secretion, in particular FGF15/19. FGFR1 expression in AGRP expressing cells is required for bile acids's ability to improve glucose control. We show that the mouse Agrp gene has 3 promoter/enhancer regions that direct transcription of each of their own AGRP transcripts. One of these Agrp promoters/enhancers, Agrp B, is regulated by bile acids. We generated an Agrp B knock-in FLP/knockout allele. AGRP B expressing cells are found in endocrine cells the pars tuberalis (PT) and co-expressDAGLB (an endocannabinoid biosynthetic enzyme), distinct from PT thyrotropes. AGRP B expression is also found in the folliculostellate cells of the pituitary's anterior lobe. Mice without AGRP B are protected from high fat feeding induced glucose intolerance but not excess weight gain. Chemogenetic inhibition of AGRP B cells improves glucose tolerance by enhancing glucose stimulated insulin secretion. Inhibition of the AGRP B cells also caused weight loss. The improved glucose tolerance and reduced body weight persisted up to 6 weeks after cessation of the DREADD mediated inhibition, suggesting the presence of a biological switch for glucose homeostasis that is regulated by long term stability of food availability.
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