OBJECTIVE: Myocardial glucose transport is enhanced by hormonal and other stimuli such as ischemia and hypoxia which induce glucose transporter 4 (GLUT4) translocation. Whether insulin and ischemia share a common signaling mechanism is not yet known. This study investigated whether phosphatidylinositol 3-kinase (PI3K), a signaling intermediate of the insulin-responsible pathway, also participates in the ischemia-induced stimulation of glucose. METHODS: Isolated Langendorff-perfused Sprague-Dawley rat hearts were subjected to 100 nmol/l insulin or 15 min of no-flow ischemia with/without 1 mumol/l wortmannin, an inhibitor of PI3K. After perfusion, relative subcellular glucose transporter GLUT4 distribution was assessed by membrane fractionation and immunoblotting and compared to controls. Uptake kinetics of the glucose analog [18F]fluoro-deoxyglucose (FDG) were also studied during perfusion of rat hearts. RESULTS: GLUT4 translocation to the plasma membrane (PM) was increased by insulin 1.8-fold and by ischemia 2.4-fold (P < 0.05). FDG uptake was increased by insulin 6.0-fold and by ischemia 6.2-fold (P < 0.05). Wortmannin 1 mumol/l inhibited insulin-mediated translocation of GLUT4 and increase in FDG uptake completely. However, it did not show any effect on ischemia-stimulated GLUT4 translocation or on ischemia-induced increase in FDG utilization. A significant correlation was found between relative GLUT4 translocation and FDG uptake in hearts of the insulin series (r = 0.9, P < 0.05) and of the ischemia series (r = 0.8, P < 0.05). CONCLUSIONS: Our results demonstrate that wortmannin did not inhibit ischemia-induced stimulation of myocardial glucose transport, supporting the hypothesis of different signaling pathways for ischemia and insulin.
OBJECTIVE:Myocardial glucose transport is enhanced by hormonal and other stimuli such as ischemia and hypoxia which induce glucose transporter 4 (GLUT4) translocation. Whether insulin and ischemia share a common signaling mechanism is not yet known. This study investigated whether phosphatidylinositol 3-kinase (PI3K), a signaling intermediate of the insulin-responsible pathway, also participates in the ischemia-induced stimulation of glucose. METHODS: Isolated Langendorff-perfused Sprague-Dawley rat hearts were subjected to 100 nmol/l insulin or 15 min of no-flow ischemia with/without 1 mumol/l wortmannin, an inhibitor of PI3K. After perfusion, relative subcellular glucose transporter GLUT4 distribution was assessed by membrane fractionation and immunoblotting and compared to controls. Uptake kinetics of the glucose analog [18F]fluoro-deoxyglucose (FDG) were also studied during perfusion of rat hearts. RESULTS:GLUT4 translocation to the plasma membrane (PM) was increased by insulin 1.8-fold and by ischemia 2.4-fold (P < 0.05). FDG uptake was increased by insulin 6.0-fold and by ischemia 6.2-fold (P < 0.05). Wortmannin 1 mumol/l inhibited insulin-mediated translocation of GLUT4 and increase in FDG uptake completely. However, it did not show any effect on ischemia-stimulated GLUT4 translocation or on ischemia-induced increase in FDG utilization. A significant correlation was found between relative GLUT4 translocation and FDG uptake in hearts of the insulin series (r = 0.9, P < 0.05) and of the ischemia series (r = 0.8, P < 0.05). CONCLUSIONS: Our results demonstrate that wortmannin did not inhibit ischemia-induced stimulation of myocardial glucose transport, supporting the hypothesis of different signaling pathways for ischemia and insulin.
Authors: Changyong Wei; Richa Bajpai; Horrick Sharma; Monique Heitmeier; Atul D Jain; Shannon M Matulis; Ajay K Nooka; Rama K Mishra; Paul W Hruz; Gary E Schiltz; Mala Shanmugam Journal: Eur J Med Chem Date: 2017-08-14 Impact factor: 6.514
Authors: E D Abel; H C Kaulbach; R Tian; J C Hopkins; J Duffy; T Doetschman; T Minnemann; M E Boers; E Hadro; C Oberste-Berghaus; W Quist; B B Lowell; J S Ingwall; B B Kahn Journal: J Clin Invest Date: 1999-12 Impact factor: 14.808
Authors: Kevin A Bybee; Joseph Murphy; Abhiram Prasad; R Scott Wright; Amir Lerman; Charanjit S Rihal; Panithaya Chareonthaitawee Journal: J Nucl Cardiol Date: 2006 Mar-Apr Impact factor: 5.952