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Reduced levels of insulin-like growth factor-1 in patients with angina pectoris, positive exercise stress test, and angiographically normal epicardial coronary arteries

      Insulin-like growth factor-1 (IGF-1) is synthesized by the liver and kidneys, and also as a paracrine and autocrine substance by endothelial cells and by vascular and cardiac myocytes.
      ,
      • Daughaday W.H.
      • Rotwein P.
      Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations.
      It has been well established that IGF-1 promotes insulin sensitivity and glucose availability to body tissues and to normal and ischemic myocardium.
      • Russell-Jones D.L.
      • Bates A.T.
      • Umpleby A.M.
      • Hennessy T.R.
      • Bowes S.B.
      • Hopkins K.D.
      • Jackson N.
      • Kelly J.
      • Shojaee-Moradie F.
      • Jones R.H.
      A comparison of the effects of IGF-1 and insulin on glucose metabolism, fat metabolism and the cardiovascular system in normal human volunteers.
      Furthermore, by enhancing tyrosine-kinase, phosphoinositol-3-kinase, and nitric oxide synthase, IGF-1 promotes nitric oxide mediated vasodilation.
      • Tsukahara H.
      • Gordienko D.V.
      • Tonshoff B.
      • Gelato M.C.
      • Goligorsky M.S.
      Direct demonstration of insulin-like growth factor-1-induced nitric oxide production by endothelial cells.
      ,
      • Osterziel K.J.
      • Bode-Boger S.M.
      • Strohm O.
      • Ellmer A.E.
      • Bit-Avragim N.
      • Hanlein D.
      • Ranke M.B.
      • Dietz R.
      • Boger R.H.
      Role of nitric oxide in the vasodilator effect of recombinant human growth hormone in patients with dilated cardiomyopathy.
      Nitric oxide inhibitors have been shown to prevent IGF-1-induced vasodilation.
      • Haylor J.
      • Singh I.
      • el Nahas A.M.
      Nitric oxide synthesis inhibitor prevents vasodilation by insulin-like growth factor 1.
      IGF-1, however, may also induce vasodilation through the opening of membrane potassium channels.
      • Sakuta H.
      Potentiation by insulin and insulin-like growth factor-1 of glibenclamide-sensitive K+ currents in follicle-enclosed Xenopus oocytes.
      Both impaired insulin sensitivity
      • Dean J.D.
      • Jones C.J.
      • Hutchison S.
      • Peters J.R.
      • Henderson A.H.
      Hyperinsulinaemia and microvascular angina (“syndrome X”).
      ,
      • Botker H.E.
      • Moller N.
      • Ovesen P.
      • Mengel A.
      • Schmitz O.
      • Oeskov H.
      • Bagger J.P.
      Insulin resistance in microvascular angina (syndrome X).
      ,
      • Chauhan A.
      • Foote J.
      • Petch M.C.
      • Schofield P.M.
      Hyperinsulinemia, coronary artery disease and syndrome X.
      ,
      • Piatti P.
      • Fragasso G.
      • Monti L.D.
      • Caumo A.
      • Van Phan C.
      • Valsecchi G.
      • Costa S.
      • Fochesato E.
      • Pozza G.
      • Pontiroli A.E.
      Endothelial and metabolic characteristics of patients with angina and angiographically normal coronary arteries comparison with subjects with insulin resistance syndrome and normal controls.
      and coronary microvascular dysfunction
      • Cannon III, R.O.
      • Epstein S.E.
      “Microvascular angina” as a cause of chest pain with angiographically normal coronary arteries.
      ,
      • Chauhan A.
      • Mullins P.A.
      • Taylor G.
      • Petch M.C.
      • Schofield P.M.
      Both endothelium-dependent and endothelium-independent function is impaired in patients with angina pectoris and normal coronary angiograms.
      have been reported in patients with cardiac syndrome X. Thus, in this study, we investigated whether abnormalities in serum IGF-1 levels are present in these patients and whether they are related to insulin levels and insulin sensitivity.
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