The GK rat beta-cell: A prototype for the diseased human beta-cell in type 2 diabetes?

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:297

Review

Portha, B.¹  Lacraz, G.¹  Kergoat, M.²  Homo-Delarche, F.¹  Giroix, M. -H.¹  Bailbe, D.¹  Gangnerau, M. -N.¹  Dolz, M.¹  Tourrel-Cuzin, C.¹  Movassat, J.¹ 

[1] Univ Paris Diderot, CNRS, Lab Physiopathol Nutr, Grp Biol & Pathol Pancreas Endocrine,UMR 7059, F-75251 Paris 05, France

[2] Ctr Rech, MERCK SERONO, Chilly Mazarin, France

关键词: Type 2 diabetes;    GK rat;    Beta-cell;    Development;    Neogenesis;    Glucotoxicity;    Inflammation;    Oxidative stress;    Insulin secretion;    Metabolic programming;    Genetic;    Epigenetic;   

DOI  :  10.1016/j.mce.2008.06.013

来源: Elsevier

【 摘 要 】

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. (C) 2008 Published by Elsevier Ireland Ltd.

【 授权许可】

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