PMID- 15926190
OWN - NLM
STAT- MEDLINE
DCOM- 20060120
LR  - 20051026
IS  - 1520-7552 (Print)
IS  - 1520-7552 (Linking)
VI  - 21
IP  - 6
DP  - 2005 Nov-Dec
TI  - Programmed disorders of beta-cell development and function as one cause for type 
      2 diabetes? The GK rat paradigm.
PG  - 495-504
AB  - Now that the reduction in beta-mass has been clearly established in humans with 
      type 2 diabetes mellitus (T2DM) 1-4, the debate focuses on the possible 
      mechanisms responsible for decreased beta-cell number and impaired beta-cell 
      function and their multifactorial etiology. Appropriate inbred rodent models are 
      essential tools for identification of genes and environmental factors that 
      increase the risk of abnormal beta-cell function and of T2DM. The information 
      available in the Goto-Kakizaki (GK) rat, one of the best characterized animal 
      models of spontaneous T2DM, are reviewed in such a perspective. We propose that 
      the defective beta-cell mass and function in the GK model reflect the complex 
      interactions of three pathogenic players: (1) several independent loci containing 
      genes causing impaired insulin secretion; (2) gestational metabolic impairment 
      inducing a programming of endocrine pancreas (decreased beta-cell neogenesis) 
      which is transmitted to the next generation; and (3) secondary (acquired) loss of 
      beta-cell differentiation due to chronic exposure to hyperglycemia 
      (glucotoxicity). An important message is that the 'heritable' determinants of 
      T2DM are not simply dependant on genetic factors, but probably involve 
      transgenerational epigenetic responses.
CI  - Copyright (c) 2005 John Wiley & Sons, Ltd.
FAU - Portha, Bernard
AU  - Portha B
AD  - Lab. Physiopathologie de la Nutrition, Universite Paris 7/D. Diderot, Paris 
      Cedex, France. portha@paris7.jussieu.fr
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Diabetes Metab Res Rev
JT  - Diabetes/metabolism research and reviews
JID - 100883450
SB  - IM
MH  - Adult
MH  - Animals
MH  - Diabetes Mellitus, Experimental/*physiopathology
MH  - Diabetes Mellitus, Type 2/*etiology/pathology/*physiopathology
MH  - Disease Models, Animal
MH  - Female
MH  - Homeostasis/physiology
MH  - Humans
MH  - Insulin-Secreting Cells/pathology/*physiology
MH  - Male
MH  - Prediabetic State/pathology
MH  - Rats
MH  - Rats, Wistar
RF  - 65
EDAT- 2005/06/01 09:00
MHDA- 2006/01/21 09:00
CRDT- 2005/06/01 09:00
PHST- 2005/06/01 09:00 [pubmed]
PHST- 2006/01/21 09:00 [medline]
PHST- 2005/06/01 09:00 [entrez]
AID - 10.1002/dmrr.566 [doi]
PST - ppublish
SO  - Diabetes Metab Res Rev. 2005 Nov-Dec;21(6):495-504. doi: 10.1002/dmrr.566.