IMPAIRED BETA-CELL FUNCTION IN THE CHINESE-HAMSTER CHIG HAN SUBLINE/

Plasma glucose and insulin levels were measured in the genetically dia betic CHIG/Han and the diabetes-resistant CHIA/Han subline of the Chin ese hamster. At 31 +/- 8 wk of age, the CHIG hamsters were grouped int o nondiabetic, mildly and severely diabetic, according to their levels of glycemia. Hyperinsulinemia, occurring in nondiabetic and mildly di abetic CHIG hamsters, was attenuated in severely diabetic animals. Lig ht microscopy and immunohistochemistry revealed initial beta-cell hype rplasia, followed by extensive degranulation and loss of immunoreactiv e insulin in islets of severely diabetic animals. Staining intensity o f glucagon-immunoreactive cells was unchanged in nondiabetic and mildl y diabetic animals, but was increased in islets from the severely diab etic hamsters. A static incubation system was used to examine the insu lin response of pancreatic islets isolated from the diabetic and nondi abetic CHIG hamsters, and the diabetes-resistant CHIA subline. Compare d with the nondiabetic CHIG hamsters, islets from mildly and severely diabetic animals displayed increased basal insulin release at 1.5 mmol /l and a deficient response at 10 mmol/l glucose which was associated with 61 and 77% decreases (p < 0.01 and p < 0.001) in the islet insuli n content. The addition of the phosphodiesterase inhibitor 3-isobutyl- 1-methylxanthine (IBMX) enhanced glucose-stimulated insulin release fr om islets of nondiabetic and mildly diabetic CHIG hamsters, although t he response elicited was lower than from CHIA islets. However, IBMX fa iled to significantly increase the glucose-stimulated insulin response of islets from severely diabetic hamsters. A negative correlation (r = -0.73, p < 0.001, n = 48) was found between islet insulin content an d plasma glucose levels. The data suggest that the reduced secretory c apacity represents an early islet beta-cell dysfunction, and the decre ase in the insulin content contributes to the islet abnormalities in t he diabetes-susceptible CHIG hamsters.