Effect of L-dopa administration on islet monoamine oxidase activity and glucose-induced insulin release in the mouse.
Previous studies have shown that the amine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is rapidly converted to its corresponding amine, dopamine, in islet beta-cells. In the present investigation, we studied the effect of acute L-DOPA administration on islet monoamine oxidase (MAO) activity and on glucose-induced insulin secretory response in mice. It was observed that at 2 min after intravenous L-DOPA administration, there was a marked increase (+35%) in islet MAO activity, with serotonin as substrate. At 7 min, MAO activity towards dopamine was enhanced by 32% and that towards serotonin and phenylethylamine (PEA) was decreased by 23 and 25%, respectively. The inhibitor of L-aromatic amino acid decarboxylase, benserazide, abolished L-DOPA-induced changes of MAO activity, suggesting that the formed dopamine, and not L-DOPA itself, was responsible for the observed effects. At 60 min, no effect by L-DOPA administration on islet MAO activity was noticed. L-DOPA (125 or 250 mumol/kg), given together with glucose, induced a decrease in glucose-induced insulin response. L-DOPA (125 mumol/kg), given 7 min before glucose, totally suppressed glucose-induced insulin response. This inhibition was eliminated through pretreatment with benserazide. Enhancement of glucose-stimulated insulin response, after deposition of horseradish peroxidase (HRP) in beta-cell vacuolar system, was suppressed by L-DOPA. We conclude that acute L-DOPA-induced dopamine accumulation in pancreatic islets is accompanied by rapid changes in MAO activity, concomitant with an inhibitory effect on glucose-stimulated insulin response. Increased hydrogen peroxide production, following increased MAO activity, may possibly augment the inhibitory effect of dopamine accumulation on insulin release.
Lundquist
I
I
Department of Cell Biology, Faculty of Health Sciences, University of Linköping, Sweden.
Panagiotidis
G
G
Stenström
A
A
D000818:Animals; D001545:Benserazide / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007275:Injections, Intravenous; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology* / Q000378:metabolism; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D007328:Insulin; D007980:Levodopa; D001545:Benserazide; D008995:Monoamine Oxidase; D005947:Glucose