Cyclosporin enhances diabetes induced by low-dose streptozotocin treatment in mice

This study concerns the effect of a 12-day cyclosporin A (CsA) treatment (50 mg per kg per day) on “autoimmune” diabetes induced by 5 low doses (40 mg per kg per day) of streptozotocin (SZ). The SZ-treatment period was initiated 4 days after initial administration of CsA. In young (45-day) CD-1 male mice, CsA enhanced hyperglycemia, hypoinsulinemia and β-cell destruction following a multiple low-dosage SZ. Moreover, CsA did not prevent development of insulitis induced concomitantly by SZ. Similarly, CsA enhanced the “toxic” diabetes produced by a single high dose (160 mg/kg) of SZ. Furthermore, in the absence of SZ, CsA alone induced glucose intolerance, associated with β-cell degranulation and high pancreatic CsA content. The enhancement of SZ-induced diabetes by CsA may thus be due to toxicity of the immunosuppressive agent for pancreatic β cells. This side effect is noteworthy because CsA is currently being used in the therapy of human insulin-dependent diabetes.