GLUCOSE-HOMEOSTASIS IN THE NONOBESE DIABETIC MOUSE AT THE PREDIABETICSTAGE

Because few data were available on glucose homeostasis at the early pr ediabetic stage in the nonobese diabetic (NOD) mouse, we investigated glycemia, insulinemia, and pancreatic insulin content under basal cond itions in both sexes of 4-, 6-, and 8-week-old fed NOD mice, compared with sex-and age-matched fed C57BL/6 mice. We also investigated glucos e tolerance in both sexes of fasting 8-week-old NOD and C57BL/6 mice. The main results obtained under basal fed conditions, when comparing b oth strains, were lower glycemia and higher insulinemia in NOD females at all ages investigated and in NOD males (particularly at 6 weeks of age). Glucose tolerance tests showed that: 1) the blood glucose respo nse to 1 g/kg ip glucose was less sustained in both sexes of 8-week-ol d NOD mice than in their control counterparts; 2) the blood insulin re sponse to glucose (1 g/kg ip) appeared earlier in both sexes of NOD mi ce than iri sex-matched C57BL/6 mice; 3) an unusual sexual dimorphism existed in NOD mice, compared with controls, with females secreting, i n response to glucose, twice as much insulin as males; 4) dose-respons e studies (1-6 g/kg glucose) confirmed the lower increase in blood glu cose levels in both sexes of NOD mice and their unusual sexual dimorph ism in insulin secretion; and 5) glucose tolerance tests in 4- to 8-we ek-old NOD mice showed that although the sexual dimorphism in insulin secretion was not observed in 4-week-old mice, it was particularly str iking at 6 weeks of age. Taken together, these results suggest that p- cell hyperactivity exists in the NOD mouse at the early prediabetic st age, especially in NOD females.