Reduced beta-cell glucose transporter in new onset diabetic BB rats.
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 beta-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 beta-cells was only 0.48 +/- 0.06, compared to 0.91 +/- 0.02 in age-matched nondiabetic diabetes-resistant controls (P less than 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 less than 0.05). Protein A-gold labeling of GLUT-2 in beta-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 less than 0.001) and 2.87 +/- 0.24 in the nondiabetic diabetes-prone rats (P less than 0.02). Reduction in GLUT-2 correlates temporally with and may contribute to the loss of glucose-stimulated insulin secretion that precedes profound beta-cell depletion of autoimmune diabetes.
Orci
L
L
Gifford Laboratories, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.
Unger
R H
RH
Ravazzola
M
M
Ogawa
A
A
Komiya
I
I
Baetens
D
D
Lodish
H F
HF
Thorens
B
B
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D009004:Monosaccharide Transport Proteins; D005947:Glucose