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Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
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Mitogen-activated protein kinase kinase inhibition does not block the stimulation of glucose utilization by insulin

D F Lazar1, R J Wiese, M J Brady

  • 1Department of Signal Transduction, Parke-Davis Pharmaceutical Research Division, Ann Arbor, Michigan 48105, USA.

The Journal of Biological Chemistry
|September 1, 1995
PubMed

Insights

Insulin activates the mitogen-activated protein kinase (MAPK) pathway, but this activation is not essential for insulin

Area of Science:

  • Cellular Biology
  • Molecular Endocrinology
  • Signal Transduction

Background:

  • Insulin is a key metabolic hormone regulating glucose homeostasis.
  • Mitogen-activated protein kinase (MAPK) pathways are involved in cellular signaling.
  • The role of MAPK activation in insulin's metabolic effects requires clarification.

Purpose of the Study:

  • To investigate the role of MAPK pathway activation in insulin's metabolic actions.
  • To determine if inhibiting MAPK activation affects insulin-stimulated glucose uptake and synthesis pathways.

Main Methods:

  • Utilized the specific MEK inhibitor PD98059 to block MAPK activation.
  • Assessed insulin-stimulated MAPK activity, phosphorylation of downstream targets (pp90Rsk, c-fos), and key metabolic processes in 3T3-L1 adipocytes and L6 myotubes.
  • Measured insulin receptor autophosphorylation and phosphatidylinositol 3'-kinase activation.

Main Results:

  • PD98059 completely abolished insulin-stimulated MAPK activity and c-fos transcriptional activation.
  • Insulin receptor autophosphorylation and phosphatidylinositol 3'-kinase activation remained unaffected by PD98059.
  • PD98059 did not alter basal or insulin-stimulated glucose uptake, lipogenesis, or glycogen synthesis.
  • Insulin-stimulated glycogen synthase and protein phosphatase 1 activities were insensitive to PD98059.

Conclusions:

  • Insulin-stimulated MAPK pathway activation is not required for major metabolic effects in cultured fat and muscle cells.
  • Insulin's metabolic actions are mediated through pathways independent of MAPK activation in these cell types.

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