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PACAP Inhibits β-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent insulinotropic G-protein-coupled receptor ligand, for which morphoregulative roles in pancreatic islets have recently been suggested. Here, we evaluated the effects of pancreatic overexpression of PACAP on morphometric changes of...

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Autores principales: Inoue, Hiroaki, Shintani, Norihito, Sakurai, Yusuke, Higashi, Shintaro, Hayata-Takano, Atsuko, Baba, Akemichi, Hashimoto, Hitoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593608/
https://www.ncbi.nlm.nih.gov/pubmed/23483824
http://dx.doi.org/10.3389/fendo.2013.00027
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author Inoue, Hiroaki
Shintani, Norihito
Sakurai, Yusuke
Higashi, Shintaro
Hayata-Takano, Atsuko
Baba, Akemichi
Hashimoto, Hitoshi
author_facet Inoue, Hiroaki
Shintani, Norihito
Sakurai, Yusuke
Higashi, Shintaro
Hayata-Takano, Atsuko
Baba, Akemichi
Hashimoto, Hitoshi
author_sort Inoue, Hiroaki
collection PubMed
description Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent insulinotropic G-protein-coupled receptor ligand, for which morphoregulative roles in pancreatic islets have recently been suggested. Here, we evaluated the effects of pancreatic overexpression of PACAP on morphometric changes of islets in a severe type II diabetes model. Following cross-breeding of obese-diabetic model KKA(y) mice with mice overexpressing PACAP in their pancreatic β-cells, the resulting KKA(y) mice with or without PACAP transgene (PACAP/+:A(y)/+ or A(y)/+ mice) were fed with a high-fat diet up to the age of 11 months. Pancreatic sections from 5- to 11-month-old littermates were examined. Histomorphometric analyses revealed significant suppression of islet mass expansion in PACAP/+:A(y)/+ mice compared with A(y)/+ mice at 11 months, but no significant difference between PACAP/+ and +/+ (wild-type) mice, as previously reported. The suppressed islet mass in PACAP/+:A(y)/+ mice was due to a decrease in islet density but not islet size. In addition, the density of tiny islets (<0.001 mm(2)) and of insulin-positive clusters in ductal structures were markedly decreased in PACAP/+:A(y)/+ mice compared with A(y)/+ mice at 5 months of age. In contrast, PACAP overexpression caused no significant effects on the level of aldehyde-fuchsin reagent staining (a measure of β-cell granulation) or the volume and localization of glucagon-positive cells in the pancreas. These results support previously reported inhibitory effects of PACAP on pancreatic islet mass expansion, and suggest it has persistent suppressive effects on pancreatic islet density which may be related with ductal cell-associated islet neogenesis in type II diabetes.
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spelling pubmed-35936082013-03-12 PACAP Inhibits β-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density Inoue, Hiroaki Shintani, Norihito Sakurai, Yusuke Higashi, Shintaro Hayata-Takano, Atsuko Baba, Akemichi Hashimoto, Hitoshi Front Endocrinol (Lausanne) Endocrinology Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent insulinotropic G-protein-coupled receptor ligand, for which morphoregulative roles in pancreatic islets have recently been suggested. Here, we evaluated the effects of pancreatic overexpression of PACAP on morphometric changes of islets in a severe type II diabetes model. Following cross-breeding of obese-diabetic model KKA(y) mice with mice overexpressing PACAP in their pancreatic β-cells, the resulting KKA(y) mice with or without PACAP transgene (PACAP/+:A(y)/+ or A(y)/+ mice) were fed with a high-fat diet up to the age of 11 months. Pancreatic sections from 5- to 11-month-old littermates were examined. Histomorphometric analyses revealed significant suppression of islet mass expansion in PACAP/+:A(y)/+ mice compared with A(y)/+ mice at 11 months, but no significant difference between PACAP/+ and +/+ (wild-type) mice, as previously reported. The suppressed islet mass in PACAP/+:A(y)/+ mice was due to a decrease in islet density but not islet size. In addition, the density of tiny islets (<0.001 mm(2)) and of insulin-positive clusters in ductal structures were markedly decreased in PACAP/+:A(y)/+ mice compared with A(y)/+ mice at 5 months of age. In contrast, PACAP overexpression caused no significant effects on the level of aldehyde-fuchsin reagent staining (a measure of β-cell granulation) or the volume and localization of glucagon-positive cells in the pancreas. These results support previously reported inhibitory effects of PACAP on pancreatic islet mass expansion, and suggest it has persistent suppressive effects on pancreatic islet density which may be related with ductal cell-associated islet neogenesis in type II diabetes. Frontiers Media S.A. 2013-03-11 /pmc/articles/PMC3593608/ /pubmed/23483824 http://dx.doi.org/10.3389/fendo.2013.00027 Text en Copyright © 2013 Inoue, Shintani, Sakurai, Higashi, Hayata-Takano, Baba and Hashimoto. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Endocrinology
Inoue, Hiroaki
Shintani, Norihito
Sakurai, Yusuke
Higashi, Shintaro
Hayata-Takano, Atsuko
Baba, Akemichi
Hashimoto, Hitoshi
PACAP Inhibits β-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density
title PACAP Inhibits β-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density
title_full PACAP Inhibits β-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density
title_fullStr PACAP Inhibits β-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density
title_full_unstemmed PACAP Inhibits β-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density
title_short PACAP Inhibits β-cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density
title_sort pacap inhibits β-cell mass expansion in a mouse model of type ii diabetes: persistent suppressive effects on islet density
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593608/
https://www.ncbi.nlm.nih.gov/pubmed/23483824
http://dx.doi.org/10.3389/fendo.2013.00027
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