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Neutralizing Th2 Inflammation in Neonatal Islets Prevents β-Cell Failure in Adult IUGR Rats

Intrauterine growth restriction (IUGR) leads to development of type 2 diabetes (T2D) in adulthood. The mechanisms underlying this phenomenon have not been fully elucidated. Inflammation is associated with T2D; however, it is unknown whether inflammation is causal or secondary to the altered metaboli...

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Autores principales: Jaeckle Santos, Lane J., Li, Changhong, Doulias, Paschalis-Thomas, Ischiropoulos, Harry, Worthen, G. Scott, Simmons, Rebecca A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994952/
https://www.ncbi.nlm.nih.gov/pubmed/24408314
http://dx.doi.org/10.2337/db13-1226
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author Jaeckle Santos, Lane J.
Li, Changhong
Doulias, Paschalis-Thomas
Ischiropoulos, Harry
Worthen, G. Scott
Simmons, Rebecca A.
author_facet Jaeckle Santos, Lane J.
Li, Changhong
Doulias, Paschalis-Thomas
Ischiropoulos, Harry
Worthen, G. Scott
Simmons, Rebecca A.
author_sort Jaeckle Santos, Lane J.
collection PubMed
description Intrauterine growth restriction (IUGR) leads to development of type 2 diabetes (T2D) in adulthood. The mechanisms underlying this phenomenon have not been fully elucidated. Inflammation is associated with T2D; however, it is unknown whether inflammation is causal or secondary to the altered metabolic state. Here we show that the mechanism by which IUGR leads to the development of T2D in adulthood is via transient recruitment of T-helper 2 (Th) lymphocytes and macrophages in fetal islets resulting in localized inflammation. Although this immune response is short-lived, it results in a permanent reduction in islet vascularity and impaired insulin secretion. Neutralizing interleukin-4 antibody therapy given only in the newborn period ameliorates inflammation and restores vascularity and β-cell function into adulthood, demonstrating a novel role for Th2 immune responses in the induction and progression of T2D. In the neonatal stage, inflammation and vascular changes are reversible and may define an important developmental window for therapeutic intervention to prevent adult-onset diabetes.
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spelling pubmed-39949522015-05-01 Neutralizing Th2 Inflammation in Neonatal Islets Prevents β-Cell Failure in Adult IUGR Rats Jaeckle Santos, Lane J. Li, Changhong Doulias, Paschalis-Thomas Ischiropoulos, Harry Worthen, G. Scott Simmons, Rebecca A. Diabetes Islet Studies Intrauterine growth restriction (IUGR) leads to development of type 2 diabetes (T2D) in adulthood. The mechanisms underlying this phenomenon have not been fully elucidated. Inflammation is associated with T2D; however, it is unknown whether inflammation is causal or secondary to the altered metabolic state. Here we show that the mechanism by which IUGR leads to the development of T2D in adulthood is via transient recruitment of T-helper 2 (Th) lymphocytes and macrophages in fetal islets resulting in localized inflammation. Although this immune response is short-lived, it results in a permanent reduction in islet vascularity and impaired insulin secretion. Neutralizing interleukin-4 antibody therapy given only in the newborn period ameliorates inflammation and restores vascularity and β-cell function into adulthood, demonstrating a novel role for Th2 immune responses in the induction and progression of T2D. In the neonatal stage, inflammation and vascular changes are reversible and may define an important developmental window for therapeutic intervention to prevent adult-onset diabetes. American Diabetes Association 2014-05 2014-04-12 /pmc/articles/PMC3994952/ /pubmed/24408314 http://dx.doi.org/10.2337/db13-1226 Text en © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Islet Studies
Jaeckle Santos, Lane J.
Li, Changhong
Doulias, Paschalis-Thomas
Ischiropoulos, Harry
Worthen, G. Scott
Simmons, Rebecca A.
Neutralizing Th2 Inflammation in Neonatal Islets Prevents β-Cell Failure in Adult IUGR Rats
title Neutralizing Th2 Inflammation in Neonatal Islets Prevents β-Cell Failure in Adult IUGR Rats
title_full Neutralizing Th2 Inflammation in Neonatal Islets Prevents β-Cell Failure in Adult IUGR Rats
title_fullStr Neutralizing Th2 Inflammation in Neonatal Islets Prevents β-Cell Failure in Adult IUGR Rats
title_full_unstemmed Neutralizing Th2 Inflammation in Neonatal Islets Prevents β-Cell Failure in Adult IUGR Rats
title_short Neutralizing Th2 Inflammation in Neonatal Islets Prevents β-Cell Failure in Adult IUGR Rats
title_sort neutralizing th2 inflammation in neonatal islets prevents β-cell failure in adult iugr rats
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3994952/
https://www.ncbi.nlm.nih.gov/pubmed/24408314
http://dx.doi.org/10.2337/db13-1226
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