Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance.
Hereditary predisposition to diet-induced type 2 diabetes has not yet been fully elucidated. We recently established 2 mouse lines with different susceptibilities (resistant and prone) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2014-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3890274?pdf=render |
_version_ | 1818274510596472832 |
---|---|
author | Mototsugu Nagao Akira Asai Wataru Inaba Momoyo Kawahara Yuki Shuto Shunsuke Kobayashi Daisuke Sanoyama Hitoshi Sugihara Soroku Yagihashi Shinichi Oikawa |
author_facet | Mototsugu Nagao Akira Asai Wataru Inaba Momoyo Kawahara Yuki Shuto Shunsuke Kobayashi Daisuke Sanoyama Hitoshi Sugihara Soroku Yagihashi Shinichi Oikawa |
author_sort | Mototsugu Nagao |
collection | DOAJ |
description | Hereditary predisposition to diet-induced type 2 diabetes has not yet been fully elucidated. We recently established 2 mouse lines with different susceptibilities (resistant and prone) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced glucose intolerance-resistant [SDG-R] and -prone [SDG-P], respectively). To investigate the predisposition to HFD-induced glucose intolerance in pancreatic islets, we examined the islet morphological features and functions in these novel mouse lines. Male SDG-P and SDG-R mice were fed a HFD for 5 weeks. Before and after HFD feeding, glucose tolerance was evaluated by oral glucose tolerance test (OGTT). Morphometry and functional analyses of the pancreatic islets were also performed before and after the feeding period. Before HFD feeding, SDG-P mice showed modestly higher postchallenge blood glucose levels and lower insulin increments in OGTT than SDG-R mice. Although SDG-P mice showed greater β cell proliferation than SDG-R mice under HFD feeding, SDG-P mice developed overt glucose intolerance, whereas SDG-R mice maintained normal glucose tolerance. Regardless of whether it was before or after HFD feeding, the isolated islets from SDG-P mice showed impaired glucose- and KCl-stimulated insulin secretion relative to those from SDG-R mice; accordingly, the expression levels of the insulin secretion-related genes in SDG-P islets were significantly lower than those in SDG-R islets. These findings suggest that the innate predispositions in pancreatic islets may determine the susceptibility to diet-induced diabetes. SDG-R and SDG-P mice may therefore be useful polygenic animal models to study the gene-environment interactions in the development of type 2 diabetes. |
first_indexed | 2024-12-12T22:15:00Z |
format | Article |
id | doaj.art-d6c03bdb6bbf44e0aceccb4ce937e85d |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-12T22:15:00Z |
publishDate | 2014-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-d6c03bdb6bbf44e0aceccb4ce937e85d2022-12-22T00:10:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8472510.1371/journal.pone.0084725Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance.Mototsugu NagaoAkira AsaiWataru InabaMomoyo KawaharaYuki ShutoShunsuke KobayashiDaisuke SanoyamaHitoshi SugiharaSoroku YagihashiShinichi OikawaHereditary predisposition to diet-induced type 2 diabetes has not yet been fully elucidated. We recently established 2 mouse lines with different susceptibilities (resistant and prone) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced glucose intolerance-resistant [SDG-R] and -prone [SDG-P], respectively). To investigate the predisposition to HFD-induced glucose intolerance in pancreatic islets, we examined the islet morphological features and functions in these novel mouse lines. Male SDG-P and SDG-R mice were fed a HFD for 5 weeks. Before and after HFD feeding, glucose tolerance was evaluated by oral glucose tolerance test (OGTT). Morphometry and functional analyses of the pancreatic islets were also performed before and after the feeding period. Before HFD feeding, SDG-P mice showed modestly higher postchallenge blood glucose levels and lower insulin increments in OGTT than SDG-R mice. Although SDG-P mice showed greater β cell proliferation than SDG-R mice under HFD feeding, SDG-P mice developed overt glucose intolerance, whereas SDG-R mice maintained normal glucose tolerance. Regardless of whether it was before or after HFD feeding, the isolated islets from SDG-P mice showed impaired glucose- and KCl-stimulated insulin secretion relative to those from SDG-R mice; accordingly, the expression levels of the insulin secretion-related genes in SDG-P islets were significantly lower than those in SDG-R islets. These findings suggest that the innate predispositions in pancreatic islets may determine the susceptibility to diet-induced diabetes. SDG-R and SDG-P mice may therefore be useful polygenic animal models to study the gene-environment interactions in the development of type 2 diabetes.http://europepmc.org/articles/PMC3890274?pdf=render |
spellingShingle | Mototsugu Nagao Akira Asai Wataru Inaba Momoyo Kawahara Yuki Shuto Shunsuke Kobayashi Daisuke Sanoyama Hitoshi Sugihara Soroku Yagihashi Shinichi Oikawa Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance. PLoS ONE |
title | Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance. |
title_full | Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance. |
title_fullStr | Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance. |
title_full_unstemmed | Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance. |
title_short | Characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high-fat diet-induced glucose intolerance. |
title_sort | characterization of pancreatic islets in two selectively bred mouse lines with different susceptibilities to high fat diet induced glucose intolerance |
url | http://europepmc.org/articles/PMC3890274?pdf=render |
work_keys_str_mv | AT mototsugunagao characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance AT akiraasai characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance AT wataruinaba characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance AT momoyokawahara characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance AT yukishuto characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance AT shunsukekobayashi characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance AT daisukesanoyama characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance AT hitoshisugihara characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance AT sorokuyagihashi characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance AT shinichioikawa characterizationofpancreaticisletsintwoselectivelybredmouselineswithdifferentsusceptibilitiestohighfatdietinducedglucoseintolerance |