Prolonged exposure of pancreatic islets isolated from "pre-diabetic" non-obese diabetic mice to a high glucose concentration does not impair Beta-cell function

Abstract

In the early stages of Type 1 (insulin-dependent) diabetes mellitus patients present a deficient insulin response to glucose. The reasons for this defective response are unknown, but it has been suggested that it reflects a deleterious effect of excessive glucose stimulation on a reduced Beta-cell mass. Female non-obese diabetic (NOD) mice from our colony, at the age of 12-13 weeks, have a normal basal glycaemia but an impaired intravenous glucose tolerance test, insulitis and a defective insulin response to glucose. In order to characterize the potential effect of glucose on the Beta cells at that "pre-diabetic" stage, pancreatic islets were isolated from 12-13 week old female NOD mice. Immediately after isolation (day 0) the NOD islets displayed a defective insulin response to an acute stimulation with 16.7 mmol/l glucose. After seven days in culture at both 11 and 28 mmol/l glucose these islets showed an increased insulin release in response to an acute glucose stimulation. This increase was more pronounced in the islets cultured at 28 mmol/l glucose. Experiments performed in parallel, using islets obtained from a non-diabetes prone strain of mice (Naval Medical Research Institute, NMRI) showed that these islets had a similar insulin release in response to glucose both on day 0 and after seven days in culture at 11 mmol/l glucose. The insulin mRNA levels of NOD islets did not change over one week in culture at 11 or 28 mmol/l glucose, but culture at the high glucose concentration induced a decrease in the islet insulin content. The present data show that culture at high glucose concentrations does not impair the function of islets isolated from NOD mice. These observations make excessive glucose stimulation, as a single factor, an unlikely explanation for the defective insulin release observed in NOD islets in the "prediabetic" period. © 1991 Springer-Verlag.