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Review

Defective functional β-cell mass and Type 2 diabetes in the Goto–Kakizaki rat model

, , , , &
Pages 785-795 | Published online: 10 Jan 2014
 

Abstract

Increasing evidence indicates that decreased functional β-cell mass is the hallmark of Type 2 diabetes mellitus. Therefore, the debate focuses on the possible mechanisms responsible for abnormal islet microenvironment, decreased β-cell number, impaired β-cell function and their multifactorial etiologies. The information available on the Goto–Kakizaki/Par rat line, one of the best characterized animal models of spontaneous Type 2 diabetes mellitus, are reviewed in such a perspective. We propose that the defective β-cell mass and function in the Goto–Kakizaki/Par model reflect the complex interactions of multiple pathogenic players, including several independent loci containing genes responsible for some diabetic traits (but not decreased β-cell mass), gestational metabolic impairment inducing an epigenetic programming of the pancreas (decreased β-cell neogenesis), which is transmitted to the next generation, and loss of β-cell differentiation due to chronic exposure to hyperglycemia, inflammatory mediators, oxidative stress and perturbed islet microarchitecture.

Financial & competing interests disclosure

This work was supported by the Centre National de la Recherche Scientifique, by the French ANR (Programme Physio 2006 – Prograbeta) and by a grant from the EFSD/MSD European Foundation. G Lacraz is a recipient of a doctoral fellowship from the Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche. M Dolz received doctoral fellowships from the Fondation pour la Recherche Médicale, the Association de Langue Française pour l’Etude du Diabète et des Maladies Métaboliques and the Société Française d’Endocrinologie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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