title: Regulation of glucose transport by insulin, bombesin, and bradykinin in Swiss 3T3 fibroblasts: involvement of protein kinase C-dependent and -independent mechanisms.
abstract: Glucose transport stimulation by insulin, bombesin, and bradykinin in Swiss 3T3 fibroblasts was compared with the phosphoinositide hydrolysis effects of the same stimulants in a variety of experimental paradigms known to affect generation and/or functioning of intracellular second messengers: short- and long-term treatments with phorbol dibutyrate, that cause activation and down-regulation of protein kinase C, respectively; cell loading with high [quin2], that causes clamping of [Ca2+]i near the resting level; poisoning with pertussis toxin, that affects the GTP binding proteins of the Go/Gi class; treatment with Ca2+ ionophores. Glucose transport stimulation by maximal [insulin] was affected by neither pertussis toxin nor protein kinase C down-regulation. The latter, however, partially blocked the action of suboptimal [insulin]; moreover, acute phorbol dibutyrate treatment caused responses more than additive at all [insulin]. Thus, the insulin action on glucose transport in 3T3 cells appears to be synergistically potentiated by a protein kinase C-dependent mechanism, and not directly mediated by the enzyme. This result correlates with the lack of effect of insulin on phosphoinositide hydrolysis. In contrast, part of the glucose transport responses induced by bombesin and bradykinin appeared to be mediated by protein kinase C in proportion with the stimulation induced by these peptides on the phosphoinositide hydrolysis. The protein kinase C-independent portion of the response to bradykinin was found to be inhibitable by pertussis toxin. This latter result might suggest an interaction between the bradykinin receptor and a glucose transporter, mediated by a protein of the Go/Gi class.
authors.affiliation: Department of Pharmacology, C.N.R. Center of Cytopharmacology, University of Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Dettori
authors.forename: J
authors.initials: J
authors.lastname: Meldolesi
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001839:Bombesin / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000502:physiology
chemical_list: D007328:Insulin; D010703:Phorbol Esters; D010716:Phosphatidylinositols; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D005947:Glucose; D001839:Bombesin; D001920:Bradykinin; D002118:Calcium