title: The effect of insulin on norepinephrine uptake by PC12 cells.
abstract: We have previously reported that insulin can enhance endogenous noradrenergic activity in vitro in the rat CNS. In the present study, we examined one potential mechanism underlying this effect: the ability of insulin to inhibit norepinephrine (NE) reuptake and secondarily increase its synaptic concentration. Acute (20 min) insulin treatment (0.1-10 nM) significantly inhibited specific 3H-norepinephrine uptake by rat hypothalamic slices. To ascertain whether this is a direct effect of insulin on cells that can synthesize and release norepinephrine, we studied NE uptake by the rat pheochromocytoma PC12 cell line. In PC12 cells, insulin (0.5-10 nM) inhibited NE uptake whereas the related peptide, insulin-like growth factor 1 (IGF-1), did not. Insulin did not compete with 3H-mazindol (a ligand for the NE reuptake transporter) binding to PC12 cell membranes. Thus, this effect of insulin is not due to interaction with either IGF-1 receptors or the norepinephrine transporter, but may be due to insulin interaction with its own receptor. Chronic (96-h) insulin treatment of PC12 cells also resulted in an inhibition of 3H-norepinephrine uptake, and membranes prepared from cells chronically treated with insulin bound less 3H-desipramine than control membranes. Thus, chronic insulin treatment may result in a decrease in the numbers of membrane-associated transporters. We conclude that insulin has a direct and physiological role in the modulation of synaptic norepinephrine levels by modulating reuptake by cells that synthesize and release norepinephrine.
authors.affiliation: Department of Psychology, University of Washington, Seattle.
authors.forename: D P
authors.initials: DP
authors.lastname: Figlewicz
authors.forename: K
authors.initials: K
authors.lastname: Bentson
authors.forename: I
authors.initials: I
authors.lastname: Ocrant
mesh_terms: D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008454:Mazindol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D008454:Mazindol; D003891:Desipramine; D009638:Norepinephrine