Interaction of Alloxan and Anomers of D-Glucose on Glucose-induced Insulin Secretion and Biosynthesis in Vitro

The direct effects of alloxan on glucose-induced insulin secretion and biosynthesis and the interaction of alloxan and D-glucose anomers were studied in vitro by use of isolated islets from rat pancreas. Islets were pretreated by incubation for five minutes in media containing alloxan (0.2 mg./ml.) alone or alloxan with either the α or β anomer of D-glucose (3 mg./ml.). After washing, batches of five islets were incubated in the medium supplemented with glucose (1.8 mg./ml.) for 60 minutes to observe insulin secretion and for 90 minutes to observe insulin biosynthesis. Prior exposure to alloxan alone produced marked inhibition of subsequent glucose-induced insulin secretion and biosynthesis. A significantly greater protection against these inhibitory effects of alloxan was observed by using the α anomer of D-glucose than the β anomer. The anomeric preference of D-glucose for protecting islet cells from the inhibitory effect of alloxan on glucose-induced insulin secretion and biosynthesis was similar to that for triggering insulin secretion. Possible mechanisms of the inhibitory effect of alloxan and the protective effect of D-glucose anomers in connection with those of other sugars are discussed. It is suggested that a glucoreceptor, stereospecific to the α anomer of D-glucose, may exist for both insulin secretion and biosynthesis.