Islet endocrine-cell behavior from birth onward in mice with the nonobese diabetic generic background

Background: Glucagon-producing alpha alpha cells play a crucial role during the perinatal period. Because of their peri-islet localization near the ea rly dendritic and macrophage cell infiltration, we thought it pertinent to investigate alpha -cells in greater depth in nonobese diabetic (NOD) mice, a well-recognized spontaneous model for human type I diabetes. Materials and Methods: We determined a-cell distribution (glucagon immunohi stochemistry and image analysis) and activity (real-time reverse transcript ase polymerase chain reaction [RT-PCR] and glucagon radioimmunoassay [RIA]) , in relationship to glycemia in NOD and lymphocyte-deficient NODscid mice as compared to control mice (C57BL/6) from birth onward. Results: NOD and N ODscid mice, particularly at 1 day of age, had twice as many very small isl ets ( < 2000 pixels) as C57BL/6 mice. During the postnatal period, the perc ent- ages of glucagon-positive areas in islets less than 2000 pixels were h igher in NOD mice than CT7BL/6; only a trend was found in NODscid. Pancreat ic mRNA expression and glucagon content decreased in all strains at weaning . However, before weaning, pancreatic and blood glucagon levels were signif icantly lower in NOD and NODscid compared to CT7BL/6 mice. Low basal nonfas ting glycemia was observed in all strains before weaning with some strain d ifferences: glycemia was significantly lower in NOD than C57BL/6, and highe r in NODscid than NOD and C57BL/6. Conclusion: These data suggest that, before weaning, NOD and, to some exten t NODscid pancreata contain more immature islets las reflected by their sma ll size and high percentages of glucagon-positive areas, concomitant with l ower glucagon storage and basal secretion) than C57BL/6 pancreata.