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Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion

Offspring of obese mothers suffer higher risks of type 2 diabetes due to increased adiposity and decreased β cell function. To date, the sex-differences in offspring islet insulin secretion during early life has not been evaluated extensively, particularly prior to weaning at postnatal day 21 (P21)....

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Autores principales: Casasnovas, Jose, Damron, Christopher Luke, Jarrell, James, Orr, Kara S., Bone, Robert N., Archer-Hartmann, Stephanie, Azadi, Parastoo, Kua, Kok Lim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181410/
https://www.ncbi.nlm.nih.gov/pubmed/34108935
http://dx.doi.org/10.3389/fendo.2021.658439
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author Casasnovas, Jose
Damron, Christopher Luke
Jarrell, James
Orr, Kara S.
Bone, Robert N.
Archer-Hartmann, Stephanie
Azadi, Parastoo
Kua, Kok Lim
author_facet Casasnovas, Jose
Damron, Christopher Luke
Jarrell, James
Orr, Kara S.
Bone, Robert N.
Archer-Hartmann, Stephanie
Azadi, Parastoo
Kua, Kok Lim
author_sort Casasnovas, Jose
collection PubMed
description Offspring of obese mothers suffer higher risks of type 2 diabetes due to increased adiposity and decreased β cell function. To date, the sex-differences in offspring islet insulin secretion during early life has not been evaluated extensively, particularly prior to weaning at postnatal day 21 (P21). To determine the role of maternal obesity on offspring islet insulin secretion, C57BL/6J female dams were fed chow or western diet from 4 weeks prior to mating to induce maternal obesity. First, offspring of chow-fed and obese dams were evaluated on postnatal day 21 (P21) prior to weaning for body composition, glucose and insulin tolerance, and islet phasic insulin-secretion. Compared to same-sex controls, both male and female P21 offspring born to obese dams (MatOb) had higher body adiposity and exhibited sex-specific differences in glucose tolerance and insulin secretion. The male MatOb offspring developed the highest extent of glucose intolerance and lowest glucose-induced insulin secretion. In contrast, P21 female offspring of obese dams had unimpaired insulin secretion. Using SAX-HPLC, we found that male MatOb had a decrease in pancreatic heparan sulfate glycosaminoglycan, which is a macromolecule critical for islet health. Notably, 8-weeks-old offspring of obese dams continued to exhibit a similar pattern of sex-differences in glucose intolerance and decreased islet insulin secretion. Overall, our study suggests that maternal obesity induces sex-specific changes to pancreatic HSG in offspring and a lasting effect on offspring insulin secretion, leading to the sex-differences in glucose intolerance.
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spelling pubmed-81814102021-06-08 Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion Casasnovas, Jose Damron, Christopher Luke Jarrell, James Orr, Kara S. Bone, Robert N. Archer-Hartmann, Stephanie Azadi, Parastoo Kua, Kok Lim Front Endocrinol (Lausanne) Endocrinology Offspring of obese mothers suffer higher risks of type 2 diabetes due to increased adiposity and decreased β cell function. To date, the sex-differences in offspring islet insulin secretion during early life has not been evaluated extensively, particularly prior to weaning at postnatal day 21 (P21). To determine the role of maternal obesity on offspring islet insulin secretion, C57BL/6J female dams were fed chow or western diet from 4 weeks prior to mating to induce maternal obesity. First, offspring of chow-fed and obese dams were evaluated on postnatal day 21 (P21) prior to weaning for body composition, glucose and insulin tolerance, and islet phasic insulin-secretion. Compared to same-sex controls, both male and female P21 offspring born to obese dams (MatOb) had higher body adiposity and exhibited sex-specific differences in glucose tolerance and insulin secretion. The male MatOb offspring developed the highest extent of glucose intolerance and lowest glucose-induced insulin secretion. In contrast, P21 female offspring of obese dams had unimpaired insulin secretion. Using SAX-HPLC, we found that male MatOb had a decrease in pancreatic heparan sulfate glycosaminoglycan, which is a macromolecule critical for islet health. Notably, 8-weeks-old offspring of obese dams continued to exhibit a similar pattern of sex-differences in glucose intolerance and decreased islet insulin secretion. Overall, our study suggests that maternal obesity induces sex-specific changes to pancreatic HSG in offspring and a lasting effect on offspring insulin secretion, leading to the sex-differences in glucose intolerance. Frontiers Media S.A. 2021-05-24 /pmc/articles/PMC8181410/ /pubmed/34108935 http://dx.doi.org/10.3389/fendo.2021.658439 Text en Copyright © 2021 Casasnovas, Damron, Jarrell, Orr, Bone, Archer-Hartmann, Azadi and Kua https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Casasnovas, Jose
Damron, Christopher Luke
Jarrell, James
Orr, Kara S.
Bone, Robert N.
Archer-Hartmann, Stephanie
Azadi, Parastoo
Kua, Kok Lim
Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion
title Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion
title_full Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion
title_fullStr Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion
title_full_unstemmed Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion
title_short Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion
title_sort offspring of obese dams exhibit sex-differences in pancreatic heparan sulfate glycosaminoglycans and islet insulin secretion
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181410/
https://www.ncbi.nlm.nih.gov/pubmed/34108935
http://dx.doi.org/10.3389/fendo.2021.658439
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