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1 Biology, University Paris Diderot/CNRS, Paris, France
2 United States
3 biology, CRBM, Paris, France
* To whom correspondence should be addressed. E-mail: jamileh.movassat{at}paris7.jussieu.fr.
Adult GK rat is characterized by impaired glucose-induced insulin secretion in vivo and in vitro, decreased beta-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 three weeks after birth and therefore could be considered as 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. To address this, we investigated beta cell function, insulin sensitivity and body composition in normoglyceamic prediabetic GK rats. Our results revealed that the in vivo secretory response of GK beta 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 when compared to 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 post natal nutritional environment of GK pups as demonstrated by cross fostering GK pups with non diabetic Wistar dams. In conclusion, in the GK model of T2D, beta cell dysfunction associated with increased insulin sensitivity and the alteration of body composition are proximal events which might contribute to the establishment of overt diabetes in adult GK rats.
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