Glucose transport system in UMR-106-01 osteoblastic osteosarcoma cells: regulation by insulin

Calcif Tissue Int. 1989 Jul;45(1):27-33. doi: 10.1007/BF02556657.

Abstract

Insulin is a potent stimulator of collagen synthesis and other osteoblastic cell functions. In various insulin-sensitive tissues, stimulation of glucose transport and glycolytic metabolism are hallmarks of insulin action and may play a role in insulin regulation of cellular function. However, the effects of insulin on glucose metabolism in osteoblast-like cells have not been defined. We therefore characterized 2-deoxy-D-glucose (2-DG) transport in UMR-106-01 rat osteoblastic osteosarcoma cells and examined its regulation by insulin. 2-DG (0.1 mM) uptake was shown to be linear with time over 45 minutes, temperature-sensitive, and inhibited by phloridzin. Competitive inhibition studies against other hexoses demonstrated a transport system stereospecificity for 2-DG similar to that previously demonstrated in fat and muscle cells. Kinetic analysis of 15 minute 2-DG uptake at 25 degrees C demonstrated a saturable transport mechanism with a Km (1.9 mM) similar to that observed for 2-DG transport in other tissues. Insulin stimulated 2-DG transport in a dose-related manner, with significant stimulation observed at 0.5 nM and maximal effect observed at 50 nM insulin. The stimulatory effect of insulin was reversibly inhibited by cytochalasin B (50 microM). Insulin stimulation of 2-DG transport was associated with a 1.7-fold increase in Vmax, while Km remained constant. When insulin effects on glucose transport were inhibited by the addition of 5 mM phloridzin, stimulatory effects on DNA and collagen synthesis were diminished, suggesting that stimulation of glucose transport may play a role in insulin effects on replication and function in osteoblast-like cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / physiopathology
  • Glucose / metabolism
  • Glucose / pharmacokinetics*
  • Insulin / metabolism
  • Insulin / pharmacology
  • Insulin / physiology*
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteoblasts / ultrastructure
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Osteosarcoma / ultrastructure
  • Phenotype
  • Rats
  • Tumor Cells, Cultured

Substances

  • Insulin
  • Glucose