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Islet Structure and Function in the GK Rat

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The Islets of Langerhans

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 654))

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 islet abnormalities so far identified is proposed in this perspective. The pathogenesis of defective β-cell number and function in the GK model is also discussed. It is proposed that the development of T2D in the GK model results from the complex interaction of multiple events: (i) several susceptibility loci containing genes responsible for some diabetic traits (distinct loci encoding impairment of β-cell metabolism and insulin exocytosis, but no quantitative trait locus for decreased β-cell mass); (ii) gestational metabolic impairment inducing an epigenetic programming of the offspring pancreas (decreased β-cell neogenesis and proliferation) transmitted over generations; and (iii) loss of β-cell differentiation related to chronic exposure to hyperglycaemia/hyperlipidaemia, islet inflammation, islet oxidative stress, islet fibrosis and perturbed islet vasculature.

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Acknowledgments

The GK/Par studies done at Lab B2PE, BFA Unit have been funded by the CNRS, the French ANR (programme Physio 2006 – Prograbeta), the EFSD/MSD European Foundation, MERCK-SERONO, French Diabetes Association and NEB Research Foundation. G. Lacraz and F. Figeac received a doctoral fellowship from the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche (Ecole Doctorale 394, Physiologie/Physiopathologie). A. Chavey was the recipient of a CNRS postdoctoral fellowship and a NESTLE-France grant.

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  1. Laboratoire B2PE, Unité BFA, Université Paris-Diderot et CNRS EAC4413, Bâtiment BUFFON – 5ème étage – pièce 552A, 4, Rue Lagroua Weill-Hallé, Case 7126, F - 75205, Paris Cedex13, France

    Bernard Portha

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

    Grégory Lacraz, Audrey Chavey, Florence Figeac, Magali Fradet, Cécile Tourrel-Cuzin, Françoise Homo-Delarche, Marie-Héléne Giroix, Danièle Bailbé, Marie-Noëlle Gangnerau & Jamileh Movassat

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Correspondence to Bernard Portha .

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    Md. Shahidul Islam

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Portha, B. et al. (2010). Islet Structure and Function in the GK Rat. In: Islam, M. (eds) The Islets of Langerhans. Advances in Experimental Medicine and Biology, vol 654. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3271-3_21

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