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

Diabetologia. 1991 Jan;34(1):6-11. doi: 10.1007/BF00404017.


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.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • DNA / analysis
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / physiopathology*
  • Female
  • Insulin / genetics
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / physiopathology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • Prediabetic State / genetics
  • Prediabetic State / physiopathology*
  • RNA, Messenger / analysis
  • Reference Values


  • Insulin
  • RNA, Messenger
  • DNA