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

Diabetes. 2001 Feb:50 Suppl 1:S89-93. doi: 10.2337/diabetes.50.2007.s89.

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 beta-cell in the GK/Par rat. In terms of beta-cell function, there is no major intrinsic secretory defect in the prediabetic GK/Par beta-cell, and the lack of beta-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 beta-cell population, the earliest alteration so far detected in the GK/Par rat targets the size of the beta-cell population. Several convergent data suggest that the permanently reduced beta-cell mass in the GK/Par rat reflects a limitation of beta-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 beta-cell development.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Count
  • Cell Survival*
  • DNA / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Female
  • Glucose / pharmacology
  • Glucose Transporter Type 2
  • Glucose-6-Phosphatase / genetics
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology*
  • Leucine / pharmacology
  • Male
  • Mitotic Index
  • Monosaccharide Transport Proteins
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar

Substances

  • Glucose Transporter Type 2
  • Insulin
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • DNA
  • Glucose-6-Phosphatase
  • Leucine
  • Glucose