β-cell function and viability in the spontaneously diabetic GK rat: Information from the GK/Par colony

Abstract

The GK rat model of type 2 diabetes is especially convenient to dissect the pathogenic mechanism necessary for the emergence of overt diabetes because all adult rats obtained in our department (GK/Par colony) to date have stable basal mild hyperglycemia and because overt diabetes is preceded by a period of normoglycemia, ranging from birth to weaning. The purpose of this article is to sum up the information so far available related to the biology of the β-cell in the GK/Par rat. In terms of β-cell function, there is no major intrinsic secretory defect in the prediabetic GK/Par β-cell, and the lack of β-cell reactivity to glucose (which reflects multiple intracellular abnormalities), as seen during the adult period when the GK/Par rats are overtly diabetic, represents an acquired defect (perhaps glucotoxicity). In terms of β-cell population, the earliest alteration so far detected in the GK/Par rat targets the size of the β-cell population. Several convergent data suggest that the permanently reduced β-cell mass in the GK/Par rat reflects a limitation of β-cell neogenesis during early fetal life, and it is conceivable that some genes among the set involved in GK diabetes belong to the subset of genes controlling early β-cell development.