Suppressor effect of morphine on the pancreatic polypeptide response to insulin-induced hypoglycemia in man

The effect of intravenous infusions of morphine and naloxone, alone or in combination, on basal plasma pancreatic polypeptide (PP) levels as well as on the PP response to insulin-induced hypoglycemia in normal subjects was investigated. Morphine infusion (150 micrograms/kg/120 min, intravenously) induced a progressive decrease in the basal plasma PP levels (basal value: 158 +/- 42 pg/mL; nadir, at 120 minutes: 108 +/- 26 pg/mL; P less than 0.05). In control experiments, insulin injection was followed by a 10-fold plasma PP elevation (peak: 1258 +/- 71 pg/mL). During morphine infusion, the PP response to hypoglycemia appeared consistently reduced (peak: 404 +/- 117 pg/mL, P less than 0.05 vs. control). Naloxone pretreatment (4.8 mg, intravenously) partially reversed the blocking effect of morphine on the PP secretion evoked by insulin-induced hypoglycemia (peak: 977 +/- 133 pg/mL, P less than 0.05 vs. control and morphine experiments). Similar degrees of hypoglycemia were achieved with and without morphine or naloxone. The intravenous infusion of naloxone alone failed to significantly modify both basal circulating PP levels and the PP response to hypoglycemia. The observation that morphine reduces PP output, both the basal value and that elicited by a parenteral stimulus, indicates that this effect is independent of its action on the gastrointestinal tract. On the other hand, the lack of effect of naloxone alone on PP secretion argues against the participation of endogenous opiates in the control of this process.