BACKGROUND: Severe myocardial hypertrophy is associated with decreased tolerance to ischemia compared with normal hearts. We hypothesized that treatment with insulin-like growth factor-1 (IGF-1) improves postischemic myocardial recovery by increasing glucose uptake during ischemia and early reperfusion. METHODS: Banding of the thoracic aorta in 10-day-old rabbits created pressure-overload hypertrophy. At 5 weeks of age (severe hypertrophy), aortic banded and sham-operated isolated hearts underwent 30 minutes of normothermic ischemia with or without IGF-1 in the preischemic perfusate and cardioplegia followed by 30 minutes of reperfusion. RESULTS: 2-Deoxyglucose uptake (31P-NMR) and phosphatidylinositol-3-kinase (PI-3-kinase) activity were significantly lower in hypertrophied hearts. Insulin-like growth factor-1 restored glucose uptake and PI-3-kinase activity to control levels in the hypertrophied hearts and both effects were blocked by wortmannin (a PI-3-kinase inhibitor). Postischemic developed pressure was significantly improved in IGF-1-treated hearts compared with untreated or IGF-1+wortmannin-treated hypertrophied hearts. CONCLUSIONS: These data indicate that IGF-1 improves glucose uptake and tolerance to ischemia in hypertrophied hearts. Myocardial IGF-1 effects are likely mediated through a PI-3-kinase-dependent pathway.
BACKGROUND: Severe myocardial hypertrophy is associated with decreased tolerance to ischemia compared with normal hearts. We hypothesized that treatment with insulin-like growth factor-1 (IGF-1) improves postischemic myocardial recovery by increasing glucose uptake during ischemia and early reperfusion. METHODS: Banding of the thoracic aorta in 10-day-old rabbits created pressure-overload hypertrophy. At 5 weeks of age (severe hypertrophy), aortic banded and sham-operated isolated hearts underwent 30 minutes of normothermic ischemia with or without IGF-1 in the preischemic perfusate and cardioplegia followed by 30 minutes of reperfusion. RESULTS:2-Deoxyglucose uptake (31P-NMR) and phosphatidylinositol-3-kinase (PI-3-kinase) activity were significantly lower in hypertrophied hearts. Insulin-like growth factor-1 restored glucose uptake and PI-3-kinase activity to control levels in the hypertrophied hearts and both effects were blocked by wortmannin (a PI-3-kinase inhibitor). Postischemic developed pressure was significantly improved in IGF-1-treated hearts compared with untreated or IGF-1+wortmannin-treated hypertrophied hearts. CONCLUSIONS: These data indicate that IGF-1 improves glucose uptake and tolerance to ischemia in hypertrophied hearts. Myocardial IGF-1 effects are likely mediated through a PI-3-kinase-dependent pathway.
Authors: Ingeborg Friehs; Hung Cao-Danh; Meena Nathan; Francis X McGowan; Pedro J del Nido Journal: Biochem Biophys Res Commun Date: 2005-05-27 Impact factor: 3.575
Authors: T Li; Y Zhao; X Yang; Y Feng; Y Li; Y Wu; M Zhang; X Li; H Hu; J Zhang; L Yuan; Y Liu; X Sun; P Qin; C Chen; D Hu Journal: J Endocrinol Invest Date: 2022-05-21 Impact factor: 4.256
Authors: Rodrigo Barillas; Ingeborg Friehs; Hung Cao-Danh; Joseph F Martinez; Pedro J del Nido Journal: Ann Thorac Surg Date: 2007-07 Impact factor: 4.330
Authors: Kazuo Kitahori; Huamei He; Mitsuhiro Kawata; Douglas B Cowan; Ingeborg Friehs; Pedro J Del Nido; Francis X McGowan Journal: Circ Heart Fail Date: 2009-09-24 Impact factor: 8.790