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.

Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I

“…Our analysis with osteoblastic cells suggests a dominant role of high affinity glucose transporters but cannot give an accurate figure since it is likely that several GLUTs account for overall glucose uptake by the cells. Thomas and co-workers [28] found a stimulatory effect of PTH on 2DG uptake in UMR cells at 1 h (and ] thymidine incorporation into DNA (lower panels) in PyMS cells exposed to PTH (left panels) or to IGF I and insulin (right panels). Cells were grown for 3 days in FCS-containing medium, rinsed with serum-free medium, and exposed for 24 h to serum-free medium.…”

“…PTH was found to increase lactate production and to decrease citrate decarboxylation by bone and osteoblastic cells [19,[24][25][26][27]. Moreover, it stimulated 2DG transport in UMR 106-01 rat osteogenic sarcoma cells after 1 h, and inhibited 2DG transport after 16 h [28]. PTH increased [ 14 C] glucose incorporation into glycogen in cultured rat calvaria cells but not in fibroblasts [6].…”

Endocrine role of bone: recent and emerging perspectives beyond osteocalcin

“…Results from in vitro studies, utilising osteoblast cultures, and in vivo studies have indicated that insulin increases bone anabolic markers, modulating collagen synthesis (Rosen & Luben 1983), alkaline phosphatase production (Canalis 1983, Kream et al 1985, Yamaguchi et al 1993, parathyroid hormone (PTH) responsiveness (Thomas et al 1995) and glucose uptake (Ituarte et al 1989). Importantly, the heterogeneous distribution of IR in neonatal rat calvaria was reported subsequently (Thomas et al 1996).…”

Fatty acid oxidation by the osteoblast is required for normal bone acquisition in a sex- and diet-dependent manner

“…This concept stems from early studies that illustrated cultured osteoblasts metabolize glucose to lactate (12)(13)(14) and that osteoanabolic hormones and growth factors stimulate glucose consumption (15,16). Recent studies have confirmed these findings using more refined genetic and molecular techniques and elaborated on mechanisms of glucose acquisition and utilization (17)(18)(19)(20).…”