The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis.
The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis.
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DOI：
10.1172/jci164185
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发表时间：
2023-04-03
影响因子：
15.9
通讯作者：
Chua Jr, Streamson
中科院分区：
文献类型：
--
作者：
Liu, Shun-Mei;Ifebi, Bruno;Johnson, Fred;Xu, Alison;Ho, Jacquelin;Yang, Yunlei;Schwartz, Gary;Jo, Young Hwan;Chua Jr, Streamson
Glucose homeostasis can be improved after bariatric surgery, which alters bile flow and stimulates gut hormone secretion, particularly FGF15/19. FGFR1 expression in AGRP-expressing cells is required for bile acids’ 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 knockin FLP/knockout allele. AGRP-B–expressing cells are found in endocrine cells of the pars tuberalis and coexpress diacylglycerol lipase B — an endocannabinoid biosynthetic enzyme — distinct from pars tuberalis thyrotropes. AGRP-B expression is also found in the folliculostellate cells of the pituitary’s anterior lobe. Mice without AGRP-B were protected from glucose intolerance induced by high-fat feeding but not from excess weight gain. Chemogenetic inhibition of AGRP-B cells improved 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.
影响因子：
3.7
作者：
Lelliott CJ;Ahnmark A;Admyre T;Ahlstedt I;Irving L;Keyes F;Patterson L;Mumphrey MB;Bjursell M;Gorman T;Bohlooly-Y M;Buchanan A;Harrison P;Vaughan T;Berthoud HR;Lindén D
通讯作者：
Lindén D
影响因子：
3.7
作者：
Kaelin, Christopher B.;Cooper, Gregory M.;Sidow, Arend;Barsh, Gregory S.
通讯作者：
Barsh, Gregory S.