Diabetes enhancement and increased islet antigen expression following neonatal injections of glucose and arginine in non-obese diabetic mice.

Modulation of beta-cell antigens at birth may affect the course of type I diabetes. Since the functional state of beta cells modulates antigen expression, we investigated whether neonatal injections of glucose and arginine (G-A) influence diabetes in non-obese diabetic (NOD) mice. Two groups of 90 mice (45 female, 45 male) were injected for the first 6 days of life with G-A or saline. To determine whether these injections influenced beta cell functional maturation, isolated islets were characterized according to insulin response to glucose or arginine. Modulation of antigens for islet-cell autoantibodies (ICA antigens) was analyzed by indirect immunofluorescence using ICA-positive human sera. Variations of pancreatic glutamic acid decarboxylase 67-kD (GAD 67) mRNA were evaluated by polymerase chain reaction (PCR), hybridization with a 32P-labeled probe, and densitometry of the autoradiographic bands. Female NOD mice treated with G-A displayed diabetes earlier and with a higher incidence (P < .01) than control mice, whereas the diabetes incidence was not statistically modified in G-A-treated male NOD mice. Insulitis was more severe (P < .03) in 2-month-old G-A-treated female NOD mice than in control mice, but was not statistically modified in male NOD mice. In both sexes, ICA antigens and GAD 67 mRNA were higher in G-A-treated mice than in control mice (P < .01). Islets isolated after neonatal G-A injections exhibited improved insulin sensitivity to both stimuli (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)