Characterization of the pancreatic polypeptide response to hypoglycemia in man

The human pancreatic polypeptide (hPP) responses to insulin injection (0.05-0.1 U/kg, i.v.) and to endogenous insulin release as provoked by i.v. tolbutamide (1 g) and oral glucose administration (1.75 g/kg) have been examined. The injection of insulin or tolbutamide was followed by a marked elevation of circulating hPP which was abolished by preventing the hypoglycemic effect of these substances by intravenous glucose infusion. Atropine pre-treatment (1 mg, i.v.) also blocked the hPP responses to insulin- or tolbutamide-induced hypoglycemia. Approximately three hours after glucose ingestion, coinciding with the hypoglycemic phase of the test, there was a clear-cut increase in circulating hPP. This hPP response was blunted by impeding the blood sugar fall to sub-baseline values-by means of a glucose infusion-as well as by prior atropinization. It is concluded that: 1) The hPP secretagogue activity of both, insulin and tolbutamide is mediated by their hypoglycemic effect. 2) The elevation of circulating hPP, which occurs during the late hypoglycemic phase of an oral glucose test, is also dependent upon the blood sugar decline to sub-baseline values. 3) Under the above conditions, the hPP response to hypoglycemia can be blocked by atropine, thus indicating that it is due to activation of the cholinergic system and not to the direct effect of glucose lack at the level of the hPP-cell.