The effect of insulin-like growth factor-1 on adult rat cardiac contractility

Abstract

There is increasing evidence that insulin-like growth factor-1 (IGF-1) may play a role in both physiological and pathophysiological events in the mammalian myocardium. The present study investigated the acute effects of IGF-1 on isometric force development in isolated rat cardiac muscle and on intracellular calcium (Ca2+) handling in isolated cardiac myocytes. IGF-1 had a positive inotropic effect on rat ventricular papillary muscles increasing force development by 17.8 +/- 4.6%, 18.5 +/- 5.8% and 11.9 +/- 4.9% (n = 12-20) at concentrations of 1, 10 and 100 ng/ml respectively. Isoprenaline increased tension in these papillary muscles by 56.7 +/- 7.7% at a concentration of 100 nM (n = 22). In comparison, insulin increased papillary muscle force development by 11.6 +/- 3.2%, 17.7 +/- 4.1% and 19.7 +/- 5.6% at concentrations of 1, 10 and 100 nM respectively (n = 16-20). In the single cardiac myocyte IGF-1 increased, the peak cytosolic free Ca2+ concentration, the amplitude of the Ca2+ transient and the time to peak Ca2+ as measured with the fluorescent bioprobe Indo-1 AM. The positive inotropic response to IGF-1 by rat ventricular muscle is therefore associated with a rise in free, peak cytosolic Ca2+ in isolated cardiac myocytes. Increasing insulin concentrations (1-1000 nM) elicited a progressive elevation in isometric force and free, cytosolic Ca2+. In contrast, in the presence of IGF-1, the maximal rise in isometric force and free cytosolic Ca2+ were both observed at 10 ng/ml. Recent reports have suggested that IGF-1 may act on the mammalian myocardium when administered chronically, but this study is amongst the first to demonstrate an acute effect of IGF-I on the mammalian heart. IGF-1 may prove then to be a novel cardioactive agent in both normal and pathophysiological states.

Adipose-derived stem cells are an effective cell candidate for treatment of heart failure: an MR imaging study of rat hearts

“…HGF is believed to be involved in regeneration of various tissues, including myocardium (13,30). IGF-I is able to prevent apoptosis and to enhance cell proliferation by activating multiple signal transduction pathways (6,11). Direct injections of plasmid DNA encoding each of the growth factors into the ischemic myocardium have been shown to increase capillary density, reduce infarct size, and improve cardiac contractile function.…”

Inverse Association Between Free Insulin-Like Growth Factor-1 and Isovolumic Relaxation in Arterial Systemic Hypertension

“…35,36 Myocardial hypertrophy and interstitial fibrosis, induced by high levels of IGF-1, have been reported to induce LV diastolic dysfunction in acromegalics. [37][38][39] IGF-1 has also been reported to increase inositol 1,4,5-tris-phosphate levels 40 ; to activate tyrosine kinase phosphatase, phosphatidylinositol-3-kinase, and protein kinase C [41][42][43] ; and to increase intracellular calcium level or sensitivity, [43][44][45] suggesting another mechanism for IVRT prolongation in case of IGF-1 overproduction.…”

The heart: an end-organ of GH action

“…Very briefly, GH and IGF-I receptors are expressed in cardiac myocytes (1), and IGF-I causes hypertrophy of cultured rat cardiomyocytes (2) and delays cardiomyocyte apoptosis (3). In addition, GH and IGF-I also play a direct effect on myocardial contractility, increasing the intracellular calcium content and enhancing the calcium sensitivity of myofilaments in cardiomyocytes (4,5). The existence of a relationship between GH/IGF-I and the cardiovascular system has also been suggested by clinical studies, as reported by the increased risk for cardiovascular morbidity and mortality in both GH deficiency (GHD) and excess (6 -12).…”