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Defective morphogenesis and functional maturation in fetal islet-like cell clusters from OLETF rat, a model of NIDDM.
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MedLine Citation:
PMID:  11467419     Owner:  NLM     Status:  MEDLINE    
A failure in the compensate proliferation of pancreatic beta-cells, as the primary pathogenic event, has been reported in OLETF rat, a model of NIDDM. The aim of the present study is to define whether the beta-cell defect is attributed to the fetal stage islet development, if so, whether the defect involves down regulation of PDX-1 protein expression. Morphological changes, beta-cell function, and the expression of PDX-1 protein were examined in the cultured fetal islet-like cell clusters (ICCs) from OLETF rats along with their diabetes-resistant control counterpart LETO rats in the presence of 5.5 or 11.1mM glucose for 48, 72, 96, and 120-hr, respectively. We have observed four abnormalities in the ICCs of OLETF rats. First, a defective morphogenesis was noted during the 72 to 120-hr ICC culture, a period characterized by a dramatic increase in both beta-cell and non-beta-cell (alpha, delta, and PP) populations in control rats. This defective morphogenesis was demonstrated by a growth retardation of epithelial stratification and poor development of both beta-cell and non-beta-cell masses along with a parallel decline in relevant islet hormone contents. Second, a functional defect was characterized by failure to response to glucose during the 96 to 120-hr-cultured ICCs. Third, the ultrastructural analysis revealed a significant reduction in the number of secretory granules. Four, Western blot analysis showed a significant decrease of PDX-1 protein expression in the OLETF ICCs cultured in 11.1mM glucose for 48 to 72-hr and in 5.5mM glucose for 120-hr. Therefore, we concluded that during the fetal stage of islet development, OLETF rats exhibit both morphological and functional defects.
M Zhu; A Mizuno; Y Noma; T Murakami; M Kuwajima; K Shima; M S Lan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of experimental diabetes research     Volume:  1     ISSN:  1560-4284     ISO Abbreviation:  Int. J. Exp. Diabetes Res.     Publication Date:  2001  
Date Detail:
Created Date:  2001-07-24     Completed Date:  2001-08-09     Revised Date:  2011-06-01    
Medline Journal Info:
Nlm Unique ID:  100962067     Medline TA:  Int J Exp Diabetes Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  289-98     Citation Subset:  IM    
Research Institute for Children, Children's Hospital, Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans 70112, USA.
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MeSH Terms
Blood Glucose / analysis
Cells, Cultured
Diabetes Mellitus, Type 2 / embryology*
Glucagon / analysis
Homeodomain Proteins*
Insulin / analysis,  blood
Islets of Langerhans / abnormalities,  chemistry,  embryology*
Rats, Inbred OLETF
Time Factors
Trans-Activators / analysis
Reg. No./Substance:
0/Blood Glucose; 0/Homeodomain Proteins; 0/Trans-Activators; 0/pancreatic and duodenal homeobox 1 protein; 11061-68-0/Insulin; 9007-92-5/Glucagon

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Int J Exp Diabetes Res
ISSN: 1560-4284
Publisher: Hindawi Publishing Corporation
Article Information
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Copyright © 2000 Hindawi Publishing Corporation.
open-access: This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received Day: 29 Month: 6 Year: 2000
Accepted Day: 14 Month: 7 Year: 2000
Print publication date: Year: 2000
Volume: 1 Issue: 4
First Page: 289 Last Page: 298
ID: 2477740
PubMed Id: 11467419
Publisher Item Identifier: S1687521400000301
DOI: 10.1155/EDR.2000.289

Defective Morphogenesis and Functional Maturation in Fetal Islet-Like Cell Clusters From OLETF Rat, A Model of NIDDM
Min Zhu1
Akira Mizuno2
Yoshihiko Noma2
Takashi Murakami2
Masamichi Kuwajima2
Kenji Shima2
Michael S. Lan13 Address:
1Research Institute for ChildrenChildren's HospitalDepartments of Pediatrics and GeneticsLouisiana State University Health Sciences CenterNew OrleansLA70112USA
2Department of Laboratory MedicineTokushima University Medical SchoolTokushima CityJapan
3Research Institute for Children520 Elmwood Park Blvd. Suite 160HarahanLA70123USA

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