Modulation by AUoxan of Glucagon and Insulin Secretion in the Isolated Perfused Rat Pancreas*

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Abstract
The acute in vitro effect of alloxan on glucagon and insulin secretion from the isolated perfused rat pancreas was examined. Alloxan alone produced transient insulin secretion. Pretreatment with alloxan attenuated both the stimulatory effect of glucose on insulin secretion and the inhibitory effect of glucose on glucagon secretion. Exposure to alloxan in varying doses either partially or completely inhibited insulin secretion induced by arginine in the presence or absence of glucose. Pretreatment with alloxan produced complex effects on arginine-induced glucagon secretion. In the absence of glucose, the response of glucagon to arginine infusion was lower in the pancreas exposed to alloxan than in the control experiment. In the presence of glucose, however, an apparently augmented response of glucagon to arginine was observed after exposure to higher doses of alloxan, suggesting an impaired inhibitory effect of glucose on arginine-induced glucagon secretion. These effects of pretreatment with alloxan on glucagon secretion cannot be explained by earlier or simultaneous insulin secretion. It is suggested that alloxan acts not only on .beta.-cells, but also directly on .alpha.-cells, although the latter are less sensitive to this agent.