The role of Gq in insulin resistant cardiac hypertrophy

Summary

Principal Investigator: Patrick Yue
Abstract: The cluster of hemodynamic and biochemical abnormalities known collectively as the metabolic syndrome affects over 47 million Americans and continues to increase in prevalence. Insulin resistance (IR) is thought to be a major underlying factor for this disorder. Evidence from population-based cohorts and animal models of IR have implicated cardiac hypertrophy as a major comorbidity in this disorder. A potentially important cofactor in the development of both IR and hypertrophy is the G protein Gq. On the in vitro and in vivo level, Gq has been well documented to cause cardiac hypertrophy. Additionally, Gq is known to inhibit insulin stimulated signaling by decreasing the activity of various downstream effectors of the insulin receptor. This proposal will seek to gain insights into the role of Gq in the pathogenesis of IR and cardiac hypertrophy by combining a nongenetic animal model of IR (the fructose-fed mouse [FFM]) with cardiac-specific transgenic inactivation of Gq. Specific Aim 1: To establish the time course of IR and hypertrophy in the FFM. Specific Aim 2: To assess the effects of transgenic Gq ablation on insulin signaling and IR in the FFM. Specific Aim 3: To study the effect of Gq ablation on the MAPK signaling cascade, a major pathway leading to hypertrophy.
Funding Period: 2004-09-01 - 2007-08-31
more information: NIH RePORT

Top Publications

  1. ncbi Magnetic resonance imaging of progressive cardiomyopathic changes in the db/db mouse
    Patrick Yue
    Division of Cardiovascular Medicine, Department of Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305 5406, USA
    Am J Physiol Heart Circ Physiol 292:H2106-18. 2007
  2. pmc HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes
    Alexander J Glassford
    Department of Medicine, Stanford University Medical Center, Stanford, CA, USA
    Am J Physiol Endocrinol Metab 293:E1590-6. 2007

Scientific Experts

  • Patrick Yue
  • Alexander J Glassford
  • Ahmad Y Sheikh
  • Philip S Tsao
  • Masahiro Terashima
  • Takayasu Arai
  • Grant Hoyt
  • Euan A Ashley
  • Shirin Zarafshar
  • Feng Cao
  • David Charo
  • Joseph Wu
  • Robert C Robbins
  • Thomas Quertermous
  • Denise A Chan
  • Phillip C Yang
  • Hyung J Chun
  • Gerald M Reaven

Detail Information

Publications2

  1. ncbi Magnetic resonance imaging of progressive cardiomyopathic changes in the db/db mouse
    Patrick Yue
    Division of Cardiovascular Medicine, Department of Medicine, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA 94305 5406, USA
    Am J Physiol Heart Circ Physiol 292:H2106-18. 2007
    ..In summary, as assessed by CMR, db/db mice develop characteristic structural and functional changes consistent with cardiomyopathy...
  2. pmc HIF-1 regulates hypoxia- and insulin-induced expression of apelin in adipocytes
    Alexander J Glassford
    Department of Medicine, Stanford University Medical Center, Stanford, CA, USA
    Am J Physiol Endocrinol Metab 293:E1590-6. 2007
    ..In summary, in cultured 3T3-L1 adipocytes and differentiated MEFs, HIF-1 appears to be involved in hypoxia- and insulin-induced apelin expression...