In vitro response to interleukin-1 beta and streptozotocin in pancreatic islets isolated from male and female nonobese diabetic mice

The aim of the present study was to examine ii the islet donor gender influences the beta-cell sensitivity to possible mediators of beta-cell destruction in insulin-dependent diabetes mellitus (IDDM). We have currently addressed this issue by comparing the action of the cytokine interleukin-1 beta (IL-1 beta) and the alkylating agent streptozotocin (STZ), on isolated pancreatic islets derived from prediabetic female and male nonobese diabetic (NOD) mice. In this mouse strain the females have a much higher incidence of spontaneous IDDM than the males. Pancreatic islets were isolated from female and male mice of the same Litter, cultured for 6 days and thereafter either 5-50 U/ml IL-1 beta were added for 48 h or 1.8 mM STZ for 30 min. The cytokine exposure caused a strong increase in the medium insulin accumulation in the cultures of islets obtained from both males and females. The insulin and DNA contents were similar when comparing female and male islets before and after cytokine exposure. The male pancreatic islets exhibited a higher rate of islet glucose oxidation than islets obtained from females after IL-1 beta addition. Non-cytokine treated islets from males showed a higher insulin content compared with corresponding female islets. After IL-1 beta addition male and female islets had a similar inhibition of insulin secretion following stimulation by glucose. On the other hand, islets of both genders were equally sensitive to the inhibitory action of STZ, when studied 6 days after STZ incubation, as assessed by glucose oxidation and insulin release experiments. In conclusion the data of the present study did not demonstrate a clear gender difference in the islet beta-cell sensitivity to immune mediated suppression by IL-1 beta or alkylation damage in IDDM-prone NOD mice. However, it cannot be excluded that in vivo, under the influence of sex hormones, a decisive alteration in beta-cell sensitivity to damage might develop.