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 highly 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 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 < 0.00001), 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Wright
J R
JR
Department of Pathology and Surgery, Izaak Walton Killam Children's Hospital, Halifax, Nova Scotia, Canada.
Fraser
R B
RB
Kapoor
S
S
Cook
H W
HW
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004198:Disease Susceptibility; D005228:Fatty Acids, Essential / Q000172:deficiency*; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D013045:Species Specificity; D013311:Streptozocin; D013997:Time Factors
D001786:Blood Glucose; D005228:Fatty Acids, Essential; D013311:Streptozocin; D016572:Cyclosporine