In the searching for new substances with the capacity to protect β-cells from the toxic effects of alloxan, we evaluated the effect of l-arginine and the polyamines putrescine, spermidine and spermine in a murine experimental model of diabetes. Diabetes was induced by the i.p. injection of either 200 mg/kg (24-h experiments) or 120 mg/kg (12 days experiments) body weight. l-Arginine and polyamines were administered 10 min before or 10 min after alloxan administration, once its half-life had elapsed, respectively.

In the 24-h study, serum glucose (199.8±27.6 mg/dl) and triglyceride (54.6±4.9 mg/dl) concentrations showed a protective effect of spermine, as these parameters were not too high (P≤0.05), compared to the alloxan-treated group (415.4±47.8 and 90.2±11.6 mg/dl, respectively), and were closer to glucose (132.3±6.0 mg/dl) and similar to triglycerides (63.8±7.1 mg/dl) of the control group.

A similar pattern was observed on the parameters measured when l-arginine and polyamines were administered daily for 12 days, starting 10 min after a single alloxan administration, which provides evidence that l-arginine and polyamines are effective in impeding the increase in serum glucose, triglyceride and cholesterol concentration showed on day 3 by the alloxan-treated group, as well as a higher acinar cell regenerative capacity as determined by immunohistochemical techniques. Spermine turning out to be more effective than l-arginine, putrescine or spermidine in counteracting the marked hyperglycemia and triglyceridemia showed by the alloxan-treated group and similar in effect when evaluating cholesterolemia.

These results show a clear protective role of l-arginine and polyamines over the pancreatic β-cell, in addition to the induction of neogenesis from both ductal and acinar cells that leads to the recovery of endocrine pancreatic function in rats with experimental diabetes.