Defect of the first-phase insulin secretion to glucose stimulation in the perfused pancreas of the nonobese diabetic (NOD) mouse.
To investigate the development of impaired insulin secretion in type I diabetes mellitus, the pancreata of ICR and NOD mice (10-50 wk of age) were perfused. According to insulin responses to 30 mM glucose and to 19 mM arginine, we classified the NOD mice into four groups: those having normal insulin secretion to glucose and to arginine similar to that of control ICR mice (group 1); those with a defect in the first-phase insulin secretion to glucose stimulation but with almost normal insulin secretion to arginine, total insulin release to glucose being significantly smaller than that of group 1 (group 2); those having only a small insulin response to either stimulus, but a fasting plasma glucose level still within the normal range (group 3); and those being overtly diabetic, showing no insulin response to either stimulus (group 4). The severity of insulitis and insulin concentration of the pancreas in each group of NOD mice was well correlated with the insulin release from the perfused pancreas. These results indicate that the initial sign of B-cell damage in NOD mice is a defect of the first phase of glucose-induced insulin secretion, which is followed by a total loss of ability to respond to glucose or arginine stimulation.
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains
D001786:Blood Glucose; D007328:Insulin; D001120:Arginine; D005947:Glucose