Document Detail


The GK rat beta-cell: a prototype for the diseased human beta-cell in type 2 diabetes?
MedLine Citation:
PMID:  18640239     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increasing evidence indicates that decreased functional beta-cell mass is the hallmark of type 2 diabetes (T2D) mellitus. Nowadays, the debate focuses on the possible mechanisms responsible for abnormal islet microenvironment, decreased beta-cell number, impaired beta-cell function, and their multifactorial aetiologies. This review is aimed to illustrate to what extend the Goto-Kakizaki rat, one of the best characterized animal models of spontaneous T2D, has proved be a valuable tool offering sufficient commonalities to study these aspects. We propose that the defective beta-cell mass and function in the GK model reflect the complex interactions of multiple pathogenic players: (i) several independent loci containing genes responsible for some diabetic traits (but not decreased beta-cell mass); (ii) gestational metabolic impairment inducing an epigenetic programming of the pancreas (decreased beta-cell neogenesis and/or proliferation) which is transmitted to the next generation; and (iii) loss of beta-cell differentiation due to chronic exposure to hyperglycemia/hyperlipidemia, inflammatory mediators, oxidative stress and to perturbed islet microarchitecture.
Authors:
B Portha; G Lacraz; M Kergoat; F Homo-Delarche; M-H Giroix; D Bailbé; M-N Gangnerau; M Dolz; C Tourrel-Cuzin; J Movassat
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2008-07-01
Journal Detail:
Title:  Molecular and cellular endocrinology     Volume:  297     ISSN:  0303-7207     ISO Abbreviation:  Mol. Cell. Endocrinol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-22     Completed Date:  2009-02-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7500844     Medline TA:  Mol Cell Endocrinol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  73-85     Citation Subset:  IM    
Affiliation:
Groupe Biologie et Pathologie du Pancréas Endocrine, Laboratoire de Physiopathologie de la Nutrition, UMR CNRS 7059, Université Paris-Diderot/UP7, Paris, France. portha@univ-paris-diderot.fr
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MeSH Terms
Descriptor/Qualifier:
Animals
Diabetes Mellitus, Type 2 / pathology*,  physiopathology
Disease Models, Animal
Humans
Insulin-Secreting Cells / pathology*
Rats

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