Essential fatty acid deficiency prevents multiple low-dose streptozotocin-induced diabetes in naive and cyclosporin-treated low-responder murine strains

We have previously shown that essential fatty acid (EFA) deficiency prevents diabetes and ameliorates insulitis in low-dose streptozotocin (LDS)-treated male CD-1 mice. The effects of EFA deficiency on the incidence of diabetes after LDS treatment has not been examined in other strains. In contrast to nighly susceptible CD-1 mice, several other strains of mice are only partially susceptible to LDS treatment and do not 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 BALB/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. Ten EFAD and 10 control mice from each strain received LDS treatment (40 mg/kg/d 5d); 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<0.00001), and C57BL/6J (P=0.012) mice. CsA supplementation increased the severity of diabetes in LDS-treated BALB/cByJ mice (P<0.0005); however, EFA deficiency also prevented diabetes in CsA-supplemented BALB/cByJ mice. Peri-insulitis was seen in 50% of control vs 40% of EFAD DBA/2J (NS) and in 20% of control vs 0% of EFAD C57BL/6J (NS) mice. Insulitis was not seen in either of these strains. Insulitis or peri-insulitis was seen in 10% of EFAD, 25% of EFAD+CsA, 33% of control, and 80% of control+CsA BALB/cByJ mice (P<0.05). We conclude that EFA deficiency prevents LDS-induced diabetes in all three of these partially susceptible strains as well as in BALB/cByJ mice augmented with CsA. EFA deficiency was confirmed biochemically on plasma samples.