Essential fatty acid deficiency prevents multiple low-dose streptozotocin-induced diabetes in CD-1 mice.
Multiple i.p. injections of low-dose streptozotocin (40 mg/kg) produce insulitis, beta cell destruction, and diabetes in male CD-1 mice. Recent data also suggest that macrophages figure in the low-dose streptozotocin model. Because other recent studies have shown that essential fatty acid deficiency prevents autoimmune nephritis in mice, decreases the number of resident Ia-positive glomerular macrophages, and decreases the elicitation of macrophages into the glomerulus in inflammation, we examined the effect of essential fatty acid deficiency on the incidence and severity of insulitis and diabetes in CD-1 mice treated with low-dose streptozotocin. Streptozotocin-treated mice on the control diet uniformly developed diabetes (19/19). Essential fatty acid-deficient mice treated with streptozotocin did not develop diabetes (1/13). Mean plasma glucose levels for the control and essential fatty acid-deficient mice were 384.5 +/- 23.6 and 129.1 +/- 15.5 mg/dl, respectively, at the end of 1 month. To discern whether essential fatty acid deficiency prevented the streptozotocin-induced beta cell injury or the inflammatory response to injured beta cells, mice were repleted with daily injections of 99% pure methyl linoleate beginning 3 days after the last streptozotocin injection. These mice also quickly developed severe (3/4) or mild (1/4) diabetes. Histologic examination of the pancreata of control mice or repleted mice showed marked insulitis and beta cell destruction; in contrast, the pancreata of essential fatty acid-deficient mice showed preservation of beta cells and only focal mild peri-insulitis. Essential fatty acid deficiency thus prevents the insulitis and resultant diabetes in low-dose streptozotocin-treated CD-1 mice, suggesting a central role for macrophages and lipid mediators in this autoimmunity model.
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000517:prevention & control*; D005228:Fatty Acids, Essential / Q000172:deficiency*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007515:Islets of Langerhans / Q000276:immunology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D010195:Pancreatitis / Q000517:prevention & control
D005228:Fatty Acids, Essential; D000949:Histocompatibility Antigens Class II; D008041:Linoleic Acids; D019787:Linoleic Acid