ESSENTIAL FATTY-ACID DEFICIENCY PREVENTS MULTIPLE LOW-DOSE STREPTOZOTOCIN-INDUCED DIABETES IN NAIVE AND CYCLOSPORINE-TREATED LOW-RESPONDER MURINE STRAINS

We have previously shown that essential fatty acid (EFA) deficiency pr events diabetes and ameliorates insulitis in low-dose streptozotocin ( LDS)-treated male CD-1 mice, The effects of EFA deficiency on the inci dence of diabetes after LDS treatment has not been examined in other s trains. In contrast to highly susceptible CD-1 mice, several other str ains of mice are only partially susceptible to LDS treatment and do no t develop appreciable insulitis; however, the susceptibility of these strains can be markedly increased by cyclosporin A (CsA) pretreatment to reduce suppressor cell function. Weanling male B ALB/cByJ, DBA/2J, and C57BL/6J mice were placed on EFA-deficient (EFAD) or control diets for 2 months and then divided into experimental and control groups. T en EFAD and 10 control mice from each strain received LDS treatment (4 0 mg/kg/d 5 d); an additional 10 EFAD BALB/cByJ and another 10 control BALB/cByJ mice received subcutaneous CsA injections (20 mg/kg/d) for 14 days prior to and for 5 days simultaneous with LDS treatment (40 mg /kg/d 5 d). Plasma glucose levels for all mice were determined 3 times per week for 3 weeks after LDS treatment. Mean plasma glucose levels (+/-SEM) at the end of the experiment were significantly lower in the EFAD groups vs control groups in BALB/cByJ (P<0.001), DBA/2J (P<0.0000 1), and C57BL/6J (P=0.012) mice. CsA supplementation increased the sev erity of diabetes in LDS-treated BALB/cByJ mice (P<0.0005); however, E FA deficiency also prevented diabetes in CsA-supplemented BALB/cByJ mi ce. Peri-insulitis was seen in 50% of control vs 40% of EFAD DBA/2J (N S) and in 20% of control vs 0% of EFAD C57BL/6J (NS) mice. Insulitis w as not seen in either of these strains, Insulitis or peri-insulitis wa s seen in 10% of EFAD, 25% of EFAD+CsA, 33% of control, and 80% of con trol+CsA BALB/cByJ mice (P<0.05). We conclude that EFA deficiency prev ents LDS-induced diabetes in all three of these partially susceptible strains as well as in BALB/cByJ mice augmented with CsA. EFA deficienc y was confirmed biochemically on plasma samples.