Impaired glucose metabolism in the heart of obese Zucker rats after treatment with phorbol ester

Int J Obes Relat Metab Disord. 2002 Mar;26(3):327-34. doi: 10.1038/sj.ijo.0801881.


Objective: To investigate the influence of obesity on the regulation of myocardial glucose metabolism following protein kinase C (PKC) activation in obese (fa/fa) and lean (Fa/?) Zucker rats.

Design: Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) for different time periods prior to the evaluation of PKC and GLUT-4 translocation. For metabolic studies isolated hearts from 48 h starved Zucker rats were perfused with an erythrocytes-enriched buffer containing increased concentrations (10-100 nM) of PMA.

Measurements: Immunodetectable PKC isozymes and GLUT-4 were determined by Western blots. Glucose oxidation and glycolysis were evaluated by measuring the myocardial release of 14CO2 and 3H2O from [U-14C]glucose and [5-3H]glucose, respectively.

Results: PMA (200 nM) induced maximal translocation of ventricular PKCalpha from the cytosol to the membranes within 10 min. This translocation was 2-fold lower in the heart from obese rats when compared to lean rats. PMA also induced a significant translocation of ventricular GLUT-4 from the microsomal to the sarcolemmal fraction within 60 min in lean but not in obese rats. Rates of basal cardiac glucose oxidation and glycolysis in obese rats were approximately 2-fold lower than those of lean rats. Perfusion with increasing concentrations of PMA (10-100 nM) led to a significant decrease of cardiac glucose oxidation in lean but not in obese rats.

Conclusion: Our results show that in the heart of the genetically obese Zucker rat, the impairment in PKCalpha activation is in line with a diminished activation of GLUT-4 as well as with the lack of PMA effect on glucose oxidation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Biomechanical Phenomena
  • Body Weight
  • Carbon Radioisotopes
  • Cell Membrane / enzymology
  • Cytosol / enzymology
  • Enzyme Activation / drug effects
  • Female
  • Glucose / metabolism*
  • Glucose Transporter Type 4
  • Glycolysis
  • Heart / physiology
  • Isoenzymes / metabolism*
  • Kinetics
  • Monosaccharide Transport Proteins / metabolism
  • Muscle Proteins*
  • Myocardium / metabolism*
  • Obesity / metabolism*
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Zucker
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tritium


  • Carbon Radioisotopes
  • Glucose Transporter Type 4
  • Isoenzymes
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Slc2a4 protein, rat
  • Tritium
  • Protein Kinase C
  • Glucose
  • Tetradecanoylphorbol Acetate