Neuropeptide Y (NPY) and norepinephrine (NE) behave like cotransmitters in intrapancreatic adrenergic nerves. Therefore, in the isolated rat pancreas, we 1) studied and compared the effect of increasing concentrations of NE and NPY given alone on insulin secretion induced by 8.3 mM glucose and on pancreatic vascular flow rate and 2) investigated the effects of combinations of NPY and NE at low concentrations. NE induced a dose-dependent inhibition of insulin release between 1 and 50 nM (max 80%); β-cells appeared sensitive to NPY at 0.1 nM, but the maximal reduction of insulin release was comparatively weak (25–30%) at 10 nM. The study of the effect of combinations of NE and NPY at different concentrations suggests that the two neurotransmitters act in an additive way to inhibit insulin secretion. NPY (0.1–10 nM) induced a marked dose-dependent reduction of pancreatic outflow rate with a biphasic pattern between 1 and 10 nM. On the other hand, at low concentrations (1 and 2 nM), NE induced a progressive increase in pancreatic outflow rate; a clear but transient decrease could only be observed at 50 nM before a secondary increase. A combined treatment with two effective concentrations of NPY (0.1 nM) and NE (1 nM) resulted in a progressive reversal by NE of NPY's vasoconstrictive effect. We conclude that β-cell function and pancreatic vascular resistance were not affected in the same way by NPY and NE: NPY appeared to be a strong vasoconstrictor but only a slight inhibitor of insulin release, whereas NE strongly inhibited β-cells and was a comparatively poor vasoconstrictor, even able to increase vascular output at low concentration. When combined at the concentrations used, they showedinhibitory additive effects on insulin secretion but exerted opposite effects and were antagonistic on pancreatic flow rate.

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