Prolonged exposure of pancreatic islets isolated from "pre-diabetic" non-obese diabetic mice to a high glucose concentration does not impair beta-cell function.
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)
Eizirik
D L
DL
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Strandell
E
E
Sandler
S
S
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D011236:Prediabetic State / Q000235:genetics / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values
D007328:Insulin; D012333:RNA, Messenger; D004247:DNA