Regulation of glucose metabolism by insulin in cardiomyocytes
Regulacija metabolizma glukoze insulinom u kardiomiocitima
Апстракт
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 regulates GLUT4 translocation and stimulation of glycogen synthesis in CMY is through activation of the protein kinase B (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 acti...vity of both pathways is required for GLUT4 translocation in CMY. Insulin independent pathways, like AMP-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 FA oxidation 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.
Funkciju srca, tokom stanja ishemije, moguće je poboljšati stimulacijom metabolizma glukoze i usled toga nastalim smanjenjem oksidacije masnih kiselina (MK). Poremećaji u metabolizmu glukoze uzrokuju poremećaje u radu srca i dovode do kardiomiopatije. Transport glukoze u ćelije jedan je od prvih koraka u insulinom stimulisanom preuzimanju glukoze u ćelije srca-kardiomiocite (CMY). Insulinom stimulisan ulazak glukoze u ćelije odvija se uz pomoć proteina nosača koji olakšavaju transport glukoze kroz ćelijsku membranu i oni su identifikovani kao glukozni transporteri (GLUT). U CMY lokalizovani su GLUT1 i GLUT4. Insulinom stimulisano preuzimanje glukoze i sinteza glikogena u CMY, uglavnom se odvijaju signalnim putem, koji uključuje aktivaciju protein kinaze B (PKB) preko fosfoinozitol 3 kinaze (PI3K). Takođe, insulin stimuliše translokaciju GLUT4 u CMY signalnim putem pomoću fosforilacije Cbl proto-onkoproteina. Aktivnost oba signalna puta neophodna je za translokaciju GLUT4 u CMY. Insulin... nezavisni put, takodje je uključen u transport glukoze u CMY. On se ostvaruje preko aktivacije AMP-om aktivirane protein kinaze (AMPK), koju inaktiviše insulinom aktivirana PKB, što dovodi do inhibicije oksidacije MK u CMY. Aktivnosti enzima PKB i AMPK su u inverznoj relaciji tokom ishemije srca. Rasvetljavanje molekularnog mehanizma interakcije AMPK i PKB pod delovanjem insulina u CMY doprineće objašnjenju protektivne uloge insulina u procesima ishemije srca.
Кључне речи:
cardiomyocytes / glucose metabolism / insulin / signaling pathways / myocardial ischemia / kardiomiociti / metabolizam glukoze / insulin / signalni putevi / ishemija srcaИзвор:
Acta Facultatis Medicae Naissensis, 2007, 24, 1, 41-44Колекције
Институција/група
VinčaTY - JOUR AU - Sudar, Emina AU - Velebit, Jelena AU - Gluvić, Zoran AU - Lazić, Emilija AU - Isenović, Esma R. PY - 2007 UR - https://vinar.vin.bg.ac.rs/handle/123456789/10331 AB - 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 regulates GLUT4 translocation and stimulation of glycogen synthesis in CMY is through activation of the protein kinase B (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 for GLUT4 translocation in CMY. Insulin independent pathways, like AMP-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 FA oxidation 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. AB - Funkciju srca, tokom stanja ishemije, moguće je poboljšati stimulacijom metabolizma glukoze i usled toga nastalim smanjenjem oksidacije masnih kiselina (MK). Poremećaji u metabolizmu glukoze uzrokuju poremećaje u radu srca i dovode do kardiomiopatije. Transport glukoze u ćelije jedan je od prvih koraka u insulinom stimulisanom preuzimanju glukoze u ćelije srca-kardiomiocite (CMY). Insulinom stimulisan ulazak glukoze u ćelije odvija se uz pomoć proteina nosača koji olakšavaju transport glukoze kroz ćelijsku membranu i oni su identifikovani kao glukozni transporteri (GLUT). U CMY lokalizovani su GLUT1 i GLUT4. Insulinom stimulisano preuzimanje glukoze i sinteza glikogena u CMY, uglavnom se odvijaju signalnim putem, koji uključuje aktivaciju protein kinaze B (PKB) preko fosfoinozitol 3 kinaze (PI3K). Takođe, insulin stimuliše translokaciju GLUT4 u CMY signalnim putem pomoću fosforilacije Cbl proto-onkoproteina. Aktivnost oba signalna puta neophodna je za translokaciju GLUT4 u CMY. Insulin nezavisni put, takodje je uključen u transport glukoze u CMY. On se ostvaruje preko aktivacije AMP-om aktivirane protein kinaze (AMPK), koju inaktiviše insulinom aktivirana PKB, što dovodi do inhibicije oksidacije MK u CMY. Aktivnosti enzima PKB i AMPK su u inverznoj relaciji tokom ishemije srca. Rasvetljavanje molekularnog mehanizma interakcije AMPK i PKB pod delovanjem insulina u CMY doprineće objašnjenju protektivne uloge insulina u procesima ishemije srca. T2 - Acta Facultatis Medicae Naissensis T1 - Regulation of glucose metabolism by insulin in cardiomyocytes T1 - Regulacija metabolizma glukoze insulinom u kardiomiocitima VL - 24 IS - 1 SP - 41 EP - 44 UR - https://hdl.handle.net/21.15107/rcub_vinar_10331 ER -
@article{ author = "Sudar, Emina and Velebit, Jelena and Gluvić, Zoran and Lazić, Emilija and Isenović, Esma R.", year = "2007", abstract = "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 regulates GLUT4 translocation and stimulation of glycogen synthesis in CMY is through activation of the protein kinase B (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 for GLUT4 translocation in CMY. Insulin independent pathways, like AMP-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 FA oxidation 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., Funkciju srca, tokom stanja ishemije, moguće je poboljšati stimulacijom metabolizma glukoze i usled toga nastalim smanjenjem oksidacije masnih kiselina (MK). Poremećaji u metabolizmu glukoze uzrokuju poremećaje u radu srca i dovode do kardiomiopatije. Transport glukoze u ćelije jedan je od prvih koraka u insulinom stimulisanom preuzimanju glukoze u ćelije srca-kardiomiocite (CMY). Insulinom stimulisan ulazak glukoze u ćelije odvija se uz pomoć proteina nosača koji olakšavaju transport glukoze kroz ćelijsku membranu i oni su identifikovani kao glukozni transporteri (GLUT). U CMY lokalizovani su GLUT1 i GLUT4. Insulinom stimulisano preuzimanje glukoze i sinteza glikogena u CMY, uglavnom se odvijaju signalnim putem, koji uključuje aktivaciju protein kinaze B (PKB) preko fosfoinozitol 3 kinaze (PI3K). Takođe, insulin stimuliše translokaciju GLUT4 u CMY signalnim putem pomoću fosforilacije Cbl proto-onkoproteina. Aktivnost oba signalna puta neophodna je za translokaciju GLUT4 u CMY. Insulin nezavisni put, takodje je uključen u transport glukoze u CMY. On se ostvaruje preko aktivacije AMP-om aktivirane protein kinaze (AMPK), koju inaktiviše insulinom aktivirana PKB, što dovodi do inhibicije oksidacije MK u CMY. Aktivnosti enzima PKB i AMPK su u inverznoj relaciji tokom ishemije srca. Rasvetljavanje molekularnog mehanizma interakcije AMPK i PKB pod delovanjem insulina u CMY doprineće objašnjenju protektivne uloge insulina u procesima ishemije srca.", journal = "Acta Facultatis Medicae Naissensis", title = "Regulation of glucose metabolism by insulin in cardiomyocytes, Regulacija metabolizma glukoze insulinom u kardiomiocitima", volume = "24", number = "1", pages = "41-44", url = "https://hdl.handle.net/21.15107/rcub_vinar_10331" }
Sudar, E., Velebit, J., Gluvić, Z., Lazić, E.,& Isenović, E. R.. (2007). Regulation of glucose metabolism by insulin in cardiomyocytes. in Acta Facultatis Medicae Naissensis, 24(1), 41-44. https://hdl.handle.net/21.15107/rcub_vinar_10331
Sudar E, Velebit J, Gluvić Z, Lazić E, Isenović ER. Regulation of glucose metabolism by insulin in cardiomyocytes. in Acta Facultatis Medicae Naissensis. 2007;24(1):41-44. https://hdl.handle.net/21.15107/rcub_vinar_10331 .
Sudar, Emina, Velebit, Jelena, Gluvić, Zoran, Lazić, Emilija, Isenović, Esma R., "Regulation of glucose metabolism by insulin in cardiomyocytes" in Acta Facultatis Medicae Naissensis, 24, no. 1 (2007):41-44, https://hdl.handle.net/21.15107/rcub_vinar_10331 .