Reduced β-cell glucose transporter in new onset diabetic BB rats

Abstract

Previous studies from our laboratories have suggested a defect in glucose transport in islets isolated from BB rats on the first day of overt diabetes. To quantitate by immunostaining the glucose transporter of β-cells (GLUT-2) before and at the onset of autoimmune diabetes we employed an antibody to its COOH-terminal octapeptide. On the first day of overt diabetes, defined as the day the daily blood glucose first reached 200 mg/dl, the volume density ratio of GLUT-2-positive to insulin-positive β-cells was only 0.48±0.06, compared to 0.91±0.02 in age-matched nondiabetic diabetes-resistant controls (P<0.001). In age-matched nondiabetic diabetes-prone rats, most of which would have become diabetic, the ratio was 0.85±0.02, also less than the controls (P<0.05). Protein A-gold labeling of GLUT-2 in β-cells of day 1 diabetic rats revealed 2.17±0.16 gold particles per micrometer length of microvillar plasma membranes compared to 3.91±0.14 in controls (P<0.001) and 2.87±0.24 in the nondiabetic diabetes-prone rats (P<0.02). Reduction in GLUT-2 correlates temporally with and may contribute to the loss of glucose-stimulated insulin secretion that precedes profound β-cell depletion of autoimmune diabetes.