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Am J Physiol Endocrinol Metab 294: E168-E175, 2008. First published November 6, 2007; doi:10.1152/ajpendo.00501.2007
0193-1849/08 $8.00
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Follow-up of GK rats during prediabetes highlights increased insulin action and fat deposition despite low insulin secretion

Jamileh Movassat,1 Danièle Bailbé,1 Cécile Lubrano-Berthelier,1 Françoise Picarel-Blanchot,1 Eric Bertin,1 Jacques Mourot,2 and Bernard Portha1

1Unité Mixte de Recherche 7059, Centre National Pour la Recherche Scientifique and Université Paris, Diderot and 2Unité Mixte de Recherche 1079, Institut National pour la Recherche Agronomic and Ecole Nationale Superieure d'Agronomie de Rennes, St. Gilles, France

Submitted 1 August 2007 ; accepted in final form 31 October 2007

The adult Goto-Kakizaki (GK) rat is characterized by impaired glucose-induced insulin secretion in vivo and in vitro, decreased β-cell mass, decreased insulin sensitivity in the liver, and moderate insulin resistance in muscles and adipose tissue. GK rats do not exhibit basal hyperglycemia during the first 3 wk after birth and therefore could be considered prediabetic during this period. Our aim was to identify the initial pathophysiological changes occurring during the prediabetes period in this model of type 2 diabetes (T2DM). To address this, we investigated β-cell function, insulin sensitivity, and body composition in normoglycemic prediabetic GK rats. Our results revealed that the in vivo secretory response of GK β-cells to glucose is markedly reduced and the whole body insulin sensitivity is increased in the prediabetic GK rats in vivo. Moreover, the body composition of suckling GK rats is altered compared with age-matched Wistar rats, with an increase of the number of adipocytes before weaning despite a decreased body weight and lean mass in the GK rats. None of these changes appeared to be due to the postnatal nutritional environment of GK pups as demonstrated by cross-fostering GK pups with nondiabetic Wistar dams. In conclusion, in the GK model of T2DM, β-cell dysfunction associated with increased insulin sensitivity and the alteration of body composition are proximal events that might contribute to the establishment of overt diabetes in adult GK rats.

Goto-Kakizaki rat; body composition; insulin sensitivity; glucose tolerance


Address for reprint requests and other correspondence: J. Movassat, CNRS UMR 7059, Université Paris 7/D. Diderot, 2, Place Jussieu, F-75251 Paris, France (e-mail: movassat{at}paris7.jussieu.fr)






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