ALLOXAN, BUT NOT STREPTOZOTOCIN, INCREASES BLOOD PERFUSION OF PANCREATIC-ISLETS IN RATS

It has recently been shown that selective B-cell toxins alloxan and streptozotocin (STZ) possess marked effects also on the vascular system. To evaluate to what extent changes in blood perfusion of islets induced by alloxan or STZ could be of importance for diabetogenic action of these compounds, we first investigated acute effects of alloxan (75 mg/kg body wt iv) and STZ (40 mg/kg body wt iv) on both whole pancreatic blood flow (PBF) and islet blood flow (IBF) in adult rats. Alloxan caused a marked increase in IBF, which was most pronounced 3 min after administration and remained for 30 min. PBF, however, was decreased 3 min after alloxan administration but was similar to that of control animals from 10 min and onward. These two opposite effects on IBF and PBF caused the fraction of whole PBF diverted through islets to increase from approximately 10 to 50%. Pretreatment with glucose (2 g/kg body wt iv), indomethacin (3.5 mg/kg body wt iv), dimethyl sulfoxide (10 ml/kg body wt ip of a 33% solution), superoxide dismutase (SOD, 1,000 kU/kg body wt iv), N(G)-methyl-L-arginine (30 mg/kg body wt iv), theophylline (7 mg/kg body wt iv), or terbutaline (1 mg/kg body wt iv) failed to affect stimulation of IBF by alloxan observed at 3 min. SOD was found to exert a marked stimulation of IBF both when given alone and together with alloxan. Alloxan increased IBF and decreased PBF also in a syngeneic pancreaticoduodenal graft in rats but did not affect flow distribution in a perfused pancreas-duodenum preparation. The decrease in PBF observed after alloxan administration could, however, be prevented by indomethacin, dimethyl sulfoxide, and SOD, suggesting that responses to alloxan of PBF and IBF are mediated by different mechanisms. Those affecting PBF are probably local and involve free radicals and prostaglandins. The increase in IBF observed after alloxan administration, however, seems to be dependent on a humoral extrapancreatic factor, the identity of which is as yet unknown. STZ caused a slight decrease in IBF when expressed as a fraction of whole PBF but had otherwise no effects on pancreatic circulation. The present observations do not suggest that the marked acute increase in islet blood perfusion induced by alloxan contributes to preferential cytotoxicity of B-cells in vivo to this toxin.