Intrauterine growth retardation (IUGR) has been linked to the development of obesity and diabetes later in life. We have developed a model of IUGR which induces obesity and diabetes in adult rats (120 days). We hypothesize that the stress of pregnancy will precipitate the development of diabetes much earlier. Furthermore, we hypothesize that the maternal metabolic milieu will result in obese offspring with abnormalities in B-cell function. Maternal uterine arteries were ligated in pregnant rats (n=15) on day 19 of gestation (term = 21.5 d). Sham operated pregnant rats served as controls (n=14). The animals were allowed to spontaneously deliver. The animals were allowed to spontaneously deliver. Litters were culled to 6 on day 1 of life. At 8 weeks of age, IUGR females were mated (n=8). Time-dated pregnant rats served as controls (n=8). At d5 and d19 of pregnancy. OGTT's were performed. In IUGR pregnant rats, OGTT's demonstrated glucose intolerance at d19 of pregnancy but not at d5. Control pregnant rats had normal OGTT's. On d19, fasting insulin, glucose, and triglycerides were significantly higher in IUGR pregnant animals compared to Controls (p<0.001). At birth, offspring of the IUGR mothers(F2) were significantly heavier than offspring of Controls (p<0.001). F2's were fostered to normal unoperated female rats. At 45 days of age, the F2's were still significantly heavier than Controls. Pancreatic islets were harvested from pups (d 7) and periperfusion studies of the islets performed(Ramp studies). Glucose concentrations were increased in the perfusate every 2 minutes up to a maximum of 50 mM. Insulin concentrations were measured by RIA. First phase insulin secretion was significantly lower in F2's compared to Controls. However, at glucose concentrations between 30-50 mM, insulin secretion was 35% higher in islets of F2 pups compared to Controls(p<0.05). Fasting glucose and insulin concentrations did not differ between F2 and Controls. At 30 days of age, OGTT's demonstrated significant glucose intolerance (p<0.01. These studies indicate that our model of intrauterine growth retardation can induce gestational diabetes in the rat. The metabolic characteristics are very similar to that observed in the human. Offspring are obese and develop glucose intolerance early in life. We speculate that the B-cell is permanently damaged in the IUGR animal and that the stress of pregnancy induces diabetes. We further speculate that gestational diabetes induces a B-cell defect in the offspring that manifests itself early in life and later causes adult onset diabetes.