HUMAN PANCREATIC-ISLET FUNCTION AT THE ONSET OF TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

Viable human pancreatic islets isolated from a recent-onset Type 1 (insulin-dependent) diabetic patient were used to perform in vitro studies. Pre-proinsulin mRNA and insulin content, as well as insulin response were analysed. Insulin response to glucose and forskolin was completely absent in diabetic islets, as compared to control islets. Insulin content was reduced to only one-third of control values (395.0 +/- 3.5 vs 989.0 +/- 46.3 muU/islet) and 20.7 +/- 3.9 % of islets from the diabetic pancreas contained insulin-positive cells in immunofluorescence studies. Northern blot analysis revealed a severe reduction in the content of pre-proinsulin mRNA in diabetic pancreatic tissue. Our results indicate that although markedly decreased, beta cells in human pancreatic islets at the onset of Type 1 diabetes are still present. Nevertheless, pancreatic islet function is disproportionately impaired with a complete absence of an insulin response.