Islet-activating protein (IAP) is a new active substance purified from the culture medium of Bordetella pertussis. This active protein possesses a molecular weight of 77,000 and an isoelectric point of pH 7.8. The nature of IAP action is characterized by the enhancement of insulin secretory response to glucose and other stimuli. In this experiment, the effect of IAP on the secretion of immunoreactive insulin (IRI) and glucagon (IRG) was investigated in conscious normal, alloxan-treated, and depancreatized dogs. On the 8th day after IAP injection, in normal and alloxan-treated dogs during the infusion of arginine or glucose, the plasma glucose level was lower and the IRI level was significantly higher compared with the saline controls. The IRG level showed no significant difference between IAP and saline control groups of normal dogs, but in alloxan-treated dogs the IRG level was significantly lower when compared with the saline control. This effect of IAP disappeared on the 30th day after injection in normal and alloxan-treated dogs. However, in depancreatized dogs, there was no effect on plasma glucose and gastrointestinal IRG levels. Anti-IAP antibody was not detected by PHA before or after IAP injection in any dogs, although a marked increase of heart rate was observed. These findings suggest that (1) IAP had an insulinotropic effect in dogs, (2) insulin deficiency induced by alloxan was partially overcome by IAP, (3) the effect of IAP on glucagon secretion might be secondarily related to the enhancement of insulin secretion, although a direct glucagon-lowering effect in alloxan-treated dogs could not be excluded, (4) a single administration of IAP did not produce anti-IAP antibody, and (5) an increase of heart rate was observed after IAP injection.

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