title: Modulation of glucose transport by parathyroid hormone and insulin in UMR 106-01, a clonal rat osteogenic sarcoma cell line.
abstract: This study characterizes the actions of insulin and parathyroid hormone (PTH) on the glucose transport system in the rat osteogenic sarcoma cell line UMR 106-01, which expresses a number of features of the osteoblast phenotype. Using [1,2-3H]2-deoxyglucose (2-DOG) as a label, UMR 106-01 cells were shown to possess a glucose transport system which was enhanced by insulin. In contrast, PTH influenced glucose transport in a biphasic manner with a stimulatory effect at 1 h and a more potent inhibitory effect at 16 h on basal and insulin-stimulated 2-DOG transport. To explore the mechanism of PTH action, a direct agonist of cAMP-dependent protein kinase (PKA) was tested. 8-Bromo-cAMP had no acute stimulatory effect but inhibited basal and insulin-stimulated 2-DOG transport at 16 h. This result suggested that the prolonged, but not the acute, effect of PTH was mediated by the generation of cAMP. Further studies with the cell line UMR 4-7, a UMR 106-01 clone stably transfected with an inducible mutant inactive regulatory subunit of PKA, confirmed that the inhibitory but not the stimulatory effect of PTH was mediated by the PKA pathway. Northern blot data indicated that the prolonged inhibitory effects of PTH and 8-bromo-cAMP on glucose transport were likely to be mediated in part by reduction in the levels of GLUT1 (HepG2/brain glucose transporter) mRNA.
authors.affiliation: University of Melbourne Department of Medicine, St Vincent's Hospital, Fitzroy, Victoria, Australia.
authors.forename: D M
authors.initials: DM
authors.lastname: Thomas
authors.forename: S D
authors.initials: SD
authors.lastname: Rogers
authors.forename: M W
authors.initials: MW
authors.lastname: Sleeman
authors.forename: G M
authors.initials: GM
authors.lastname: Pasquini
authors.forename: F R
authors.initials: FR
authors.lastname: Bringhurst
authors.forename: K W
authors.initials: KW
authors.lastname: Ng
authors.forename: J D
authors.initials: JD
authors.lastname: Zajac
authors.forename: J D
authors.initials: JD
authors.lastname: Best
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002999:Clone Cells / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D003847:Deoxyglucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D019379:Teriparatide; D014407:Tumor Cells, Cultured
chemical_list: D051272:Glucose Transporter Type 1; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C495679:Slc2a1 protein, rat; D019379:Teriparatide; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003847:Deoxyglucose; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose