Diabetogenic effect of STZ diminishes with the loss of nitric oxide: role of ultraviolet light and carboxy-PTIO.

Nitric oxide has been demonstrated to participate in beta-cell damage during streptozotocin (STZ)-induced diabetes. STZ consists of 2-deoxy-D-glucose substituted by N-methyl-N-nitrosourea at C-2 and therefore can liberate (.) NO. However, it has not been proven whether (.) NO generation from STZ is responsible for the disease. We found that STZ treated in vitro with ultraviolet (UV) light liberated significantly more (.) NO than non-irradiated STZ (1134.4 +/- 104 vs. 256.9 +/- 240 nmol). Moreover, the diabetogenic effect of STZ was abolished by UV irradiation before its administration to experimental animals. In these animals the glucose and insulin values were significantly different from those of the diabetic group (151.3 +/- 16.6 vs. 364.6 +/- 63.4 mg/dl and 36.3 +/- 17.9 vs. 0.08 +/- 5.5 microIU/ml, respectively) and similar to those of the non-diabetic group (127.2 +/- 34.1 mg/dl and 41.7 +/- 13.9 microIU/ml, respectively). Carboxy-PTIO treatment returned glycemia to nearly normal levels in 60% of STZ-induced diabetic rats (157.5 +/- 11.8 vs. 364.6 +/- 63.6 mg/dl of the diabetic group). L-NAME and dexamethasone cannot return either glucose or insulin to normal levels. In conclusion, UV light increased (.) NO liberation from STZ and suppressed its diabetogenic activity. It is possible that the diabetogenic activity of STZ is related to the liberation of nitric oxide from STZ, since carboxy-PTIO scavenger had a protective effect, while L-NAME and dexamethasone did not. It is possible that an increase in (.) NO concentration into cell, independently of its endogenous or exogenous origin, can induce beta-cell damage and diabetes.