Presynaptic sympathetic mechanism in the insulinostatic effect of epinephrine in mouse pancreatic islets.
The catecholamines inhibit insulin release. It is not established whether presynaptic mechanisms contribute to this effect. We therefore examined the relative contribution of presynaptic and postsynaptic mechanisms to the insulinostatic effects of epinephrine and norepinephrine. Mice were injected with 6-hydroxydopamine (6-OHDA; 0.19 mmol/kg) or its vehicle. Islets were isolated after 48 h. Islets from vehicle-injected control animals contained numerous tyrosine hydroxylase (TH)-immunoreactive nerve terminals (marker for sympathetic nerves). In contrast, TH-immunoreactive nerves were not detected in islets from 6-OHDA-treated animals, indicating sympathetic denervation. Basal (5.6 mmol/l glucose) or glucose-stimulated (16.7 mmol/l) insulin secretion did not differ between incubated islets from vehicle-injected control animals and islets from 6-OHDA-treated animals. The insulinostatic effect of epinephrine, but not that of norepinephrine, was markedly impaired in islets from 6-OHDA-treated animals: the lowest effective insulinostatic concentration of epinephrine was 0.01 nmol/l in islets from vehicle-injected animals and 1 nmol/l in islets from 6-OHDA-treated animals. We conclude that in isolated mouse islets the insulinostatic effect of epinephrine, but not that of norepinephrine, partially depends on sympathetic nerve terminals, suggesting an important role for presynaptic mechanisms in epinephrine-induced inhibition of insulin secretion.
Karlsson
S
S
Department of Medicine, University Hospital of Malmö, Lund University, Sweden.
Myrsén
U
U
Nieuwenhuizen
A
A
Sundler
F
F
Ahrén
B
B
D000818:Animals; D046508:Culture Techniques; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000294:innervation / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D007328:Insulin; D009478:Neuropeptide Y; D014660:Vasoactive Intestinal Peptide; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine