Summary
Five low doses (40 mg·kg−1·day−1) of streptozotocin were given to CD-1 mice to induce “immune” diabetes with insulitis. T-splenocytes (L3T4+ and Lyt 2+) from streptozotocin-treated mice were previously reported to display in vitro an increased binding for Beta cells, preceding the onset of hyperglycaemia and of insulitis. Since heparin inhibits lymphocyte traffic, displays anti-adhesive properties, and attenuates some cell-mediated immune diseases, we have investigated the effects of heparin and N-desulphated heparin: 1) in vivo on low-dose streptozotocin-induced diabetes and insulitis, and 2) in vitro on the increased binding of T-splenocytes from streptozotocin-treated mice to rat insulinoma (RINm5F) cells. Daily subcutaneous low doses (5 μg or 10 μg) of heparin induced a delay in onset and a reduction of the severity of hyperglycaemia and insulitis (p < 0.01), and reduced the incidence of diabetes (p < 0.01). Similar effects swere obtained with 5 μg daily doses of N-desulphated heparin devoid of anticoagulant activity. In contrast, lower (1 μg) or higher (200 μg) doses of heparin were ineffective. Heparin (10 μg) did not modify the “toxic” diabetes induced by a single high dose (200 mg/kg) of streptozotocin. On the other hand, heparin dose-dependently (0.1 μg/ml to 500.0 μg/ml) inhibited the increased binding of splenocytes from streptozotocin-injected mice to RIN cells as compared to splenocytes from control mice. This in vitro anti-adhesive effect was detected when either splenocytes or RIN cells were pretreated with heparin before their co-incubation, and was also obtained with N-desulphated heparin. Heparinoids display anti-adhesive and immunomodulatory properties that are of therapeutic potential in this model of Type 1 (insulin-dependent) diabetes mellitus.
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Saï, P., Pogu, S. & Ouary, M. Heparin attenuates low-dose streptozotocin-induced immune diabetes in mice and inhibits the Beta-cell binding of T-splenocytes in vitro. Diabetologia 34, 212–217 (1991). https://doi.org/10.1007/BF00405078
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DOI: https://doi.org/10.1007/BF00405078