The anti-diabetogenic effect of essential fatty acid deficiency in multiple low-dose streptozotocin-treated mice persists if essential fatty acid repletion occurs outside of a brief window of susceptibility.
We have previously shown that essential fatty acid deficiency prevents diabetes mellitus and ameliorates insulitis in multiple low-dose streptozotocin-treated male CD-1 mice and that repletion with 99% pure methyl linoleate 3 days after the last injection causes diabetes. In the present study, we examined whether repletion of low-dose streptozotocin-treated deficient mice will cause diabetes whenever repletion occurs. Essential fatty acid deficiency was induced by dietary manipulation and was confirmed biochemically. Groups of deficient mice were repleted 6 h, 1 week, 2 weeks, 4 weeks and 8 weeks after the last low-dose streptozotocin treatment; the incidence of diabetes (i.e., non-fasting plasma glucose levels greater than 11.2 mmol/l) and group mean plasma glucose levels were 93% (19.4 mmol/l), 37% (14.8 mmol/l), 40% (13.7 mmol/l), 20% (9.0 mmol/l), and 8% (7.8 mmol/l) respectively. The incidence and mean glucose levels for low-dose streptozotocin-induced control chow-fed and non-repleted essential fatty acid deficient CD-1 mice were 100% (30.2 mmol/l) and 0% (4.2 mmol/l). The incidence and severity of insulitis also decreased with increasing repletion intervals. These results demonstrate a brief window of susceptibility of less than 8 weeks duration during which repletion will initiate an autoimmune response directed at low-dose streptozotocin-induced Beta-cell neoantigens in low-dose streptozotocin-treated essential fatty acid deficient mice.
Wright
J R
JR
Department of Pathology, Izaak Walton Killam Children's Hospital, Halifax, Nova Scotia, Canada.
Haliburton
B
B
Russell
H
H
Henry
M
M
Fraser
R
R
Cook
H W
HW
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology* / Q000517:prevention & control*; D004041:Dietary Fats; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D005228:Fatty Acids, Essential / Q000172:deficiency*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013311:Streptozocin / Q000008:administration & dosage; D013997:Time Factors
D001786:Blood Glucose; D004041:Dietary Fats; D005228:Fatty Acids, Essential; D005230:Fatty Acids, Nonesterified; D013311:Streptozocin