Authors: Portha, Bernard; Lacraz, G; Dolz, M; Homo-Delarche, F; Giroix, M-H; Movassat, J

Source: Expert Review of Endocrinology and Metabolism, Volume 2, Number 6, November 2007 , pp. 785-795(11)

Publisher: Expert Reviews

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.

Keywords: β-cell; development; epigenetic; genetic; glucotoxicity; Goto-Kakizaki rat; inflammation; metabolic programming; neogenesis; oxidative stress; Type 2 diabetes

Document Type: Research article

DOI: http://dx.doi.org/10.1586/17446651.2.6.785

Publication date: 2007-11-01

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• Expert Review of Endocrinology & Metabolism provides extensive coverage of state-of-the-art research and clinical advancements in the field of endocrine control and metabolism, with a focus on screening, prevention, diagnostics, existing and novel therapeutics, as well as related molecular genetics, pathophysiology and epidemiology
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