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The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis
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/e...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065075/ https://www.ncbi.nlm.nih.gov/pubmed/36787185 http://dx.doi.org/10.1172/JCI164185 |
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author | Liu, Shun-Mei Ifebi, Bruno Johnson, Fred Xu, Alison Ho, Jacquelin Yang, Yunlei Schwartz, Gary Jo, Young Hwan Chua, Streamson |
author_facet | Liu, Shun-Mei Ifebi, Bruno Johnson, Fred Xu, Alison Ho, Jacquelin Yang, Yunlei Schwartz, Gary Jo, Young Hwan Chua, Streamson |
author_sort | Liu, Shun-Mei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10065075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-100650752023-04-03 The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis Liu, Shun-Mei Ifebi, Bruno Johnson, Fred Xu, Alison Ho, Jacquelin Yang, Yunlei Schwartz, Gary Jo, Young Hwan Chua, Streamson J Clin Invest Research Article 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. American Society for Clinical Investigation 2023-04-03 /pmc/articles/PMC10065075/ /pubmed/36787185 http://dx.doi.org/10.1172/JCI164185 Text en © 2023 Liu et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Liu, Shun-Mei Ifebi, Bruno Johnson, Fred Xu, Alison Ho, Jacquelin Yang, Yunlei Schwartz, Gary Jo, Young Hwan Chua, Streamson The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis |
title | The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis |
title_full | The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis |
title_fullStr | The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis |
title_full_unstemmed | The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis |
title_short | The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis |
title_sort | gut signals to agrp-expressing cells of the pituitary to control glucose homeostasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10065075/ https://www.ncbi.nlm.nih.gov/pubmed/36787185 http://dx.doi.org/10.1172/JCI164185 |
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