Relation between alloxan-induced plasma membrane dysfunction and inhibition of insulin secretion in pancreatic B-cells in vivo.

The acute effects of alloxan on plasma membrane function and insulin content of pancreatic B-cells were investigated in vivo. Rats received a single injection of alloxan, 75 mg/kg b.w. intravenously. The animals were sacrificed up to 24 h after treatment. The membrane damage was evaluated by a dye-exclusion test, demonstrating cells unable to exclude Evans blue/albumin (EBA) complexes. The insulin content was demonstrated by immunofluorescence. The alloxan injection resulted in a transient decrease in insulin content, later followed by a sustained increase, indicating inhibition of secretion. Increased levels of insulin were evident 50 min after alloxan treatment, and concomitantly an increasing number of injured, i.e. EBA-positive, cells could be demonstrated in the islets. Inhibition of insulin secretion appeared to precede inhibition of insulin synthesis as well as development of membrane dysfunction. It is suggested that the early inhibition of insulin secretion, induced by alloxan, is due to interference with cytoplasmic sulfhydryl and disulfide containing proteins.