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.

Abstract

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.

• Authors: J R Wright Jr, B Haliburton, H Russell, M Henry, R Fraser, H W Cook
• Journal: Diabetologia (Diabetologia) Vol. 34 Issue 10 Pg. 709-14 (Oct 1991) ISSN: 0012-186X [Print] Germany
• PMID: 1835705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Dietary Fats
• Fatty Acids, Essential
• Fatty Acids, Nonesterified
• Streptozocin

Topics

• Animals
• Blood Glucose (metabolism)
• Diabetes Mellitus, Experimental (blood, physiopathology, prevention & control)
• Dietary Fats
• Disease Susceptibility
• Dose-Response Relationship, Drug
• Fatty Acids, Essential (deficiency)
• Fatty Acids, Nonesterified (blood)
• Male
• Mice
• Mice, Inbred Strains
• Streptozocin (administration & dosage)
• Time Factors