Stimulation of pancreatic polypeptide and glucagon secretion by 2-deoxy-D-glucose in man: evidence for cholinergic mediation.
Hypoglycemia is known to stimulate human pancreatic polypeptide (hPP) secretion. To explore further the relationship between glucose availability and hPP release, we have examined the effect of tissue glucopenia induced by 2-deoxy-D-glucose (2-DG) on hPP plasma levels in normal subjects. As this glucose analogue activates the autonomic nervous system, we have also studied the influence of prior atropinization upon the hPP response to 2-DG. Moreover, we have tested the effects of iv epinephrine and norepinephrine on plasma hPP concentrations. Circulating glucagon was also measured. After the iv infusion of 2-DG (50 mg/kg), plasma hPP increased steeply from a fasting value of 104 +/- 24 pg/ml (SEM) to a peak of 2175 +/- 639 pg/ml at 45 min (P less than 0.01) and remained significantly elevated throughout the test. In contrast, prior injection of atropine (1 mg iv) lowered basal hPP levels and reduced conspicuously the hPP response to 2-DG. Epinephrine administration (6 micrograms/min for 60 min) did not significantly modify plasma hPP concentrations. However, 2 h after epinephrine withdrawal, circulating hPP showed a brisk elevation coinciding with the decline of glycemia to subbaseline values. During norepinephrine infusion (6 micrograms/min for 60 min), only a minor and transient increase of plasma hPP was found. Plasma glucagon rose significantly after 2-DG infusion, but this response was virtually absent in the atropine experiment. Whereas the well known glucagon tropic activity of epinephrine was evidenced, norepinephrine failed to exert an obvious effect on glucagonemia. Our data demonstrate that 2-DG induces a powerful stimulation of hPP secretion in normal subjects and suggest that this action is mediated in part, if not entirely, by the parasympathetic nervous system. On the other hand, a major role of the sympathoadrenal system in response of hPP to 2-DG or to hypoglycemia does not seem probable. Finally, the hyperglucagonemic effect of 2-DG seems also to be dependent on cholinergic transmission.
D000328:Adult; D001285:Atropine; D003837:Deoxy Sugars; D003847:Deoxyglucose; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D007700:Kinetics; D009638:Norepinephrine; D010191:Pancreatic Polypeptide / Q000097:blood / Q000378:metabolism*; D012016:Reference Values
D003837:Deoxy Sugars; D007328:Insulin; D010191:Pancreatic Polypeptide; D001285:Atropine; D005934:Glucagon; D003847:Deoxyglucose; D009638:Norepinephrine