GLUT-2 function in glucose-unresponsive beta cells of dexamethasone-induced diabetes in rats.
Spontaneous and dexamethasone-induced noninsulin-dependent diabetes mellitus (NIDDM) in rats is associated with loss of glucose-stimulated insulin secretion (GSIS) and a reduction in both GLUT-2-positive beta cells and high Km glucose transport. To determine if the chronology and correlation of these abnormalities is consistent with a causal relationship, Zucker (fa/fa) rats were studied longitudinally before and during 10 d of dexamethasone-induced (0.4 mg/kg per d i.p.) NIDDM. Within 24 h of dexamethasone treatment blood glucose rose and GSIS declined, becoming paradoxically negative (-87 +/- 12 microU/ml per min) on day 10. Blood glucose was negatively correlated with GSIS (r = -0.92; P < 0.001). 3-0-methyl-D-glucose (3MG) transport was unchanged at 12 h, 23% below normal on day 1, and declined further to a nadir 59% below normal. The GLUT-2-positive beta cell area did not decline until 48 h, reaching a nadir of 35% of normal at 10 d. The area of GLUT-2-positive beta cells was correlated with GSIS (r = 0.77; P < 0.005). We conclude that the chronology and correlation between GSIS loss and hyperglycemia is consistent with a cause-effect relationship, but that the subtotal impairment in glucose transport by itself cannot explain the total loss of GSIS if one assumes that normal beta cells are functionally homogenous.
Ohneda
M
M
Department of Internal Medicine and Pathology, University of Texas Southwestern Medical Center, Dallas 75235.
Johnson
J H
JH
Inman
L R
LR
Unger
R H
RH
D019325:3-O-Methylglucose; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003907:Dexamethasone / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology*; D051273:Glucose Transporter Type 2; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008757:Methylglucosides / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker
D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D007328:Insulin; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D019325:3-O-Methylglucose; D015735:Mifepristone; D003907:Dexamethasone; D001120:Arginine; D005947:Glucose