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The GK Rat: A Prototype for the Study of Non-overweight Type 2 Diabetes

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Book cover Animal Models in Diabetes Research

Part of the book series: Methods in Molecular Biology ((MIMB,volume 933))

Abstract

Type 2 diabetes mellitus (T2D) arises when the endocrine pancreas fails to secrete sufficient insulin to cope with the metabolic demand because of β-cell secretory dysfunction and/or decreased β-cell mass. Defining the nature of the pancreatic islet defects present in T2D has been difficult, in part because human islets are inaccessible for direct study. This review is aimed to illustrate to what extent the Goto Kakizaki rat, one of the best characterized animal models of spontaneous T2D, has proved to be a valuable tool offering sufficient commonalities to study this aspect. A comprehensive compendium of the multiple functional GK abnormalities so far identified is proposed in this perspective, together with their time-course and interactions. A special focus is given toward the pathogenesis of defective β-cell number and function in the GK model. It is proposed that the development of T2D in the GK model results from the complex interaction of multiple events: (1) several susceptibility loci containing genes responsible for some diabetic traits; (2) gestational metabolic impairment inducing an epigenetic programming of the offspring pancreas and the major insulin target tissues; and (3) environmentally induced loss of β-cell differentiation due to chronic exposure to hyperglycemia/hyperlipidemia, inflammation, and oxidative stress.

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Acknowledgments

The GK/Par studies done at Lab B2PE, BFA Unit, have been funded by the CNRS, the University Paris-Diderot, the French ANR (programme Physio 2006—Prograbeta), the EFSD/MSD European Foundation, SERVIER, MERCK-SERONO, NOVO-Nordisk, PFIZER, MetaBrain Research, NESTLE-France, the SFD/French Diabetes Association, the FRM/Medical Research Foundation and NEB Research Foundation.

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  1. Laboratoire B2PE (Biologie et Pathologie du Pancréas Endocrine), Unité BFA (Biologie Fonctionnelle et Adaptive), Université Paris-Diderot, CNRS EAC 4413, Paris, France

    Bernard Portha, Marie-Hélène Giroix, Cecile Tourrel-Cuzin, Hervé Le-Stunff & Jamileh Movassat

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  1. Bernard Portha
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  2. Marie-Hélène Giroix
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  3. Cecile Tourrel-Cuzin
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  4. Hervé Le-Stunff
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  5. Jamileh Movassat
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Correspondence to Bernard Portha .

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Editors and Affiliations

  1. , Department of Pharmacology, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Germany

    Hans-Georg Joost

  2. German Diabetes Centre, Clinical Biochemistry &Pathobiochemistry, Heinrich Heine University Düsseldorf, Auf'm Hennekamp 65, Düsseldorf, 40225, Germany

    Hadi Al-Hasani

  3. , Department of Experimental Diabetology, German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, Nuthetal, 14558, Germany

    Annette Schürmann

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Portha, B., Giroix, MH., Tourrel-Cuzin, C., Le-Stunff, H., Movassat, J. (2012). The GK Rat: A Prototype for the Study of Non-overweight Type 2 Diabetes. In: Joost, HG., Al-Hasani, H., Schürmann, A. (eds) Animal Models in Diabetes Research. Methods in Molecular Biology, vol 933. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-068-7_9

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