The effect of alloxan on the permeability of isolated pancreatic islets to horseradish peroxidase.

The effect of alloxan on the permeability of isolated pancreatic islets to horseradish peroxidase was studied by a perifusion system, which allowed simultaneous monitoring of glucose-induced insulin secretion. Rat islets were perifused with a 5 mg/ml glucose solution containing horseradish peroxidase for ten or thirty minutes, with or without prior exposure to alloxan (20 mg%) for five minutes. Control islets without alloxan treatment showed few necrotic beta cells diffusely infiltrated with exogenous peroxidase; and, the majority were intact beta cells containing numerous peroxidase-positive vesicles. Islets purifused with alloxan in a 1 mg/ml glucose solution showed many damaged beta cells loaded with peroxidase; whereas, intact beta cells contained a few peroxidase-positive vesicles. In islets purifused with alloxan in a 5 mg/ml glucose solution, the features seen in the control islets and the islets purifused with alloxan in a 1 mg/ml glucose solution were observed--namely, degenerated beta cells loaded with peroxidase and intact beta cells with numberous peroxidase-positive vesicles. As the guinea pig is known to be relatively resistant to the effect of alloxan, the effect of alloxan was examined in the isolated islets of guinea pig. The degenerated peroxidase-positive beta cells were not observed in guinea pig islets, which had been exposed to alloxan (20 mg%). It is concluded that the direct alloxan action on rat beta cells is at least partially to damage beta cell membranes with resultant enhanced permeability to horseradish peroxidase.