ACTA FAC.
MED. NAISS. 2007; 24 (1): 33-40|
ACTA FAC.
MED. NAISS. 2007; 24 (1): 33-40 |
Professional article
REGULATION OF GLUCOSE METABOLISM BY INSULIN IN CARDIOMYOCYTES
Emina Sudar1 , Jelena Velebit1,
Zoran Gluvic2, Emilija Lazic1, Esma R. Isenovic1
1Institute of Nuclear Sciences „VINČA“, Belgrade, Serbia
2Clinical Hospital Center Zemun-Belgrade, Zemun, Serbia
SUMMARY
Cardiac function is improved during ischemia by stimulating glucose metabolism and subsequent decreasing of fatty acid (FA) oxidation. The impairment of heart glucose metabolism may contribute to the heart dysfunction and cardiomyopathy. Glucose transport is one of the first steps in insulin stimulated glucose uptake. Glucose entry into cells is a process that requires the involvement of a carrier protein in order to facilitate the movement of glucose across the plasma membrane. In cardiomyocytes (CMY), insulin stimulated glucose disposal is mediated via translocation of glucose transporters (GLUTs): GLUT4 and GLUT1.
The major mechanism by which insulin regulatesGLUT4translocation and stimulation of glycogen synthesis in CMY is through activation of the protein kinaseB(PKB via phosphoinositol 3 kinase (PI3-K). In addition, insulin stimulates GLUT4 translocation and increases glucose uptake in CMY via PI3- K independent pathway by Cbl proto-oncoprotein phosphorylation. Combined activity of both pathways is required forGLUT4translocation inCMY. Insulin independent pathways, likeAMP-activated protein kinase (AMPK) pathway, also contributes to increased glucose uptake in CMY and PKB, and AMPK activity are inversely correlated during myocardial ischemia, although the influence of insulin on AMPK cardiac signaling would contradict previous observations. It has been reported that via PKB, insulin has an ability to inactivate AMPK. Inhibition of AMPK by insulin may be a contributory mechanism to the observation that cardiac FAoxidation is inhibited by insulin. Understanding how these two kinases interact at the molecular level in response to insulin may provide insights into how insulin is cardioprotective against ischemia.
Key words: cardiomyocytes, glucose metabolism, insulin, signaling pathways, myocardial ischemia