A New Model for the Study of Mild Diabetes During Pregnancy: Syngeneic Islet-Transplanted STZ-Induced Diabetic Rats

Abstract

Diabetes during pregnancy carries short- and long-term consequences for the offspring. Improved obstetrical and diabetic care has resulted in decreased morbidity and mortality in the neonate of the diabetic mother. Mild hyperglycemia is still found in both IDDM pregnant women and women with GDM. The long-term consequences of exposure to mild hyperglycemia in utero remain to be determined. In an effort to develop an appropriate animal model of mild diabetes during pregnancy, we mated female STZ-induced diabetic rats previously transplanted with specific numbers of islets of Langerhans (2500,1000, 700, or 500 islets). Diabetic and nondiabetic sham-transplanted control groups also were studied. During pregnancy, the plasma glucose levels in the diabetic rats and the group receiving 500 islets (26.5 ± 1.1 and 10.0 ± 0.8 mM, respectively) were significantly greater than in control animals (5.4 ± 0.5 mM, P < 0.0001). The mean glucose levels in rats receiving 700 or 1000 transplanted islets (6.8 ± 0.2 and 6.5 ± 0.2 mM) also were significantly greater than in control animals (P < 0.001). No difference was evident between control rats and the group receiving 2500 islets (5.8 ± 0.2 mM). No gross congenital abnormalities were apparent in the offspring. The pup plasma glucose was significantly greater in the offspring of dams receiving either none (diabetic) or 500 islets (10.6 ± 0.7 and 11.1 ± 1.1 mM, respectively) compared with the offspring of nondiabetic control dams (4.4 ± 0.3 mM, P < 0.0001). The pup pancreatic insulin content was lower in the offspring of diabetic animals than in control animals (4.9 ± 0.3 vs. 15.2 ± 0.5 nM/mg, P < 0.0001), but no difference was found between the offspring of islet-transplanted dams compared with control offspring. In summary, the STZ-induced diabetic rat transplanted with a specified number of islets of Langerhans is a promising new animal model for the study of mild to moderate hyperglycemia during pregnancy. This model should be useful for study of the longer term consequences of diabetes during pregnancy.