title: Hyperglycemia in vitro attenuates insulin-stimulated chemokinesis in normal human neutrophils. Role of protein kinase C activation.
abstract: This study was performed to test whether the inhibitory effect of elevated D-glucose concentrations on insulin-stimulated chemokinesis in normal human neutrophils is mediated by increase in protein kinase C (PKC) activity. Activation of PKC with phorbol 12-myristate 13-acetate (PMA) at 0-100 nM dose-dependently inhibited neutrophil random locomotion in the absence of insulin. Sub-optimal concentrations of PMA (0.1-0.5 nM) inhibited the chemokinetic effect of 160 microU/mL insulin in a dose-dependent way. The specific PKC inhibitor bisindolylmaleimide (GF 109203x) did not affect the insulin-stimulated chemokinesis at 5 mM glucose but restored the chemokinetic effect of insulin at 15 mM glucose. These results therefore suggest that glucose-induced PKC activation may mediate the inhibitory effects of high glucose levels on insulin-stimulated chemokinesis in normal human neutrophils.
authors.affiliation: Department of Histology and Cell Biology, Umeå University, Sweden. per-arne.oldenborg@histocel.umu.se
authors.forename: P A
authors.initials: PA
authors.lastname: Oldenborg
authors.forename: J
authors.initials: J
authors.lastname: Sehlin
mesh_terms: D000328:Adult; D002465:Cell Movement / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000097:blood* / Q000201:enzymology; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D007328:Insulin; D008301:Maleimides; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate