Glucose- and Bile Acid-Stimulated Secretion of Gut Hormones in the Isolated Perfused Intestine Is Not Impaired in Diet-Induced Obese Mice

PurposeDecreased circulating levels of food-intake-regulating gut hormones have been observed in type 2 diabetes and obesity. However, it is still unknown if this is due to decreased secretion from the gut mucosal cells or due to extra-intestinal processing of hormones.MethodsWe measured intestinal...

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Main Authors: Jenna E. Hunt, Jens J. Holst, Sara L. Jepsen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2022.884501/full
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author Jenna E. Hunt
Jenna E. Hunt
Jens J. Holst
Jens J. Holst
Sara L. Jepsen
Sara L. Jepsen
author_facet Jenna E. Hunt
Jenna E. Hunt
Jens J. Holst
Jens J. Holst
Sara L. Jepsen
Sara L. Jepsen
author_sort Jenna E. Hunt
collection DOAJ
description PurposeDecreased circulating levels of food-intake-regulating gut hormones have been observed in type 2 diabetes and obesity. However, it is still unknown if this is due to decreased secretion from the gut mucosal cells or due to extra-intestinal processing of hormones.MethodsWe measured intestinal hormone content and assessed morphological differences in the intestinal mucosa by histology and immunohistochemistry. Secretion of hormones and absorption of glucose and bile acids (BA) were assessed in isolated perfused mouse intestine.ResultsGIP (glucose-dependent insulinotropic polypeptide) and SS (somatostatin) contents were higher in the duodenum of control mice (p < 0.001, and <0.01). Duodenal GLP-1 (glucagon-like peptide-1) content (p < 0.01) and distal ileum PYY content were higher in DIO mice (p < 0.05). Villus height in the jejunum, crypt depth, and villus height in the ileum were increased in DIO mice (p < 0.05 and p = 0.001). In the distal ileum of DIO mice, more immunoreactive GLP-1 and PYY cells were observed (p = 0.01 and 0.007). There was no difference in the absorption of glucose and bile acids. Distal secretion of SS tended to be higher in DIO mice (p < 0.058), whereas no difference was observed for the other hormones in response to glucose or bile acids.ConclusionOur data suggest that differences regarding production and secretion are unlikely to be responsible for the altered circulating gut hormone levels in obesity, since enteroendocrine morphology and hormone secretion capacity were largely unaffected in DIO mice.
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spelling doaj.art-bd5e0f71eee34dcebd1236778b7b9f0f2022-12-22T00:44:01ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-05-011310.3389/fendo.2022.884501884501Glucose- and Bile Acid-Stimulated Secretion of Gut Hormones in the Isolated Perfused Intestine Is Not Impaired in Diet-Induced Obese MiceJenna E. Hunt0Jenna E. Hunt1Jens J. Holst2Jens J. Holst3Sara L. Jepsen4Sara L. Jepsen5Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkPurposeDecreased circulating levels of food-intake-regulating gut hormones have been observed in type 2 diabetes and obesity. However, it is still unknown if this is due to decreased secretion from the gut mucosal cells or due to extra-intestinal processing of hormones.MethodsWe measured intestinal hormone content and assessed morphological differences in the intestinal mucosa by histology and immunohistochemistry. Secretion of hormones and absorption of glucose and bile acids (BA) were assessed in isolated perfused mouse intestine.ResultsGIP (glucose-dependent insulinotropic polypeptide) and SS (somatostatin) contents were higher in the duodenum of control mice (p < 0.001, and <0.01). Duodenal GLP-1 (glucagon-like peptide-1) content (p < 0.01) and distal ileum PYY content were higher in DIO mice (p < 0.05). Villus height in the jejunum, crypt depth, and villus height in the ileum were increased in DIO mice (p < 0.05 and p = 0.001). In the distal ileum of DIO mice, more immunoreactive GLP-1 and PYY cells were observed (p = 0.01 and 0.007). There was no difference in the absorption of glucose and bile acids. Distal secretion of SS tended to be higher in DIO mice (p < 0.058), whereas no difference was observed for the other hormones in response to glucose or bile acids.ConclusionOur data suggest that differences regarding production and secretion are unlikely to be responsible for the altered circulating gut hormone levels in obesity, since enteroendocrine morphology and hormone secretion capacity were largely unaffected in DIO mice.https://www.frontiersin.org/articles/10.3389/fendo.2022.884501/fulldiabetesdiet-induced obesitygut hormonesobesityincretinPYY
spellingShingle Jenna E. Hunt
Jenna E. Hunt
Jens J. Holst
Jens J. Holst
Sara L. Jepsen
Sara L. Jepsen
Glucose- and Bile Acid-Stimulated Secretion of Gut Hormones in the Isolated Perfused Intestine Is Not Impaired in Diet-Induced Obese Mice
Frontiers in Endocrinology
diabetes
diet-induced obesity
gut hormones
obesity
incretin
PYY
title Glucose- and Bile Acid-Stimulated Secretion of Gut Hormones in the Isolated Perfused Intestine Is Not Impaired in Diet-Induced Obese Mice
title_full Glucose- and Bile Acid-Stimulated Secretion of Gut Hormones in the Isolated Perfused Intestine Is Not Impaired in Diet-Induced Obese Mice
title_fullStr Glucose- and Bile Acid-Stimulated Secretion of Gut Hormones in the Isolated Perfused Intestine Is Not Impaired in Diet-Induced Obese Mice
title_full_unstemmed Glucose- and Bile Acid-Stimulated Secretion of Gut Hormones in the Isolated Perfused Intestine Is Not Impaired in Diet-Induced Obese Mice
title_short Glucose- and Bile Acid-Stimulated Secretion of Gut Hormones in the Isolated Perfused Intestine Is Not Impaired in Diet-Induced Obese Mice
title_sort glucose and bile acid stimulated secretion of gut hormones in the isolated perfused intestine is not impaired in diet induced obese mice
topic diabetes
diet-induced obesity
gut hormones
obesity
incretin
PYY
url https://www.frontiersin.org/articles/10.3389/fendo.2022.884501/full
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