GLUT2 EXPRESSION AND FUNCTION IN BETA-CELLS OF GK RATS WITH NIDDM - DISSOCIATION BETWEEN REDUCTIONS IN GLUCOSE-TRANSPORT AND GLUCOSE-STIMULATED INSULIN-SECRETION

GLUT2 underexpression has been reported in the beta-cells of Zucker di abetic fatty rats and db/db mice, models of spontaneously occurring NI DDM with antecedent obesity. To determine whether the beta-cells of a nonobese rodent model of NIDDM exhibit the same abnormalities in GLUT2 , we studied Goto-Kakizaki rats. In these mildly diabetic animals gluc ose-stimulated insulin secretion was reduced at all ages examined from 8 to 48 wk. In normal control Wistar rats, immunostainable GLUT2 was present on all insulin-positive cells in the pancreatic islets. Only 8 5% of beta-cells were GLUT2-positive in GK rats at 12 wk of age, and o nly 34% were positive at 48 wk of age. GLUT2 mRNA was 50% of normal in 12-wk-old GK rats. In the latter age-group, glucose-stimulated insuli n secretion was only 28% of normal at a time when 85% of beta-cells we re GLUT2-positive and initial 3-O-methyl-D-glucose transport rate was 77% of the control value. We conclude that although GLUT2 is underexpr essed, neither the magnitude of the underexpression of GLUT2 nor of th e reduction in GLUT2 transport function in islets of GK rats is suffic ient by itself to explain the profound reduction in glucose-stimulated insulin secretion.