The effect of insulin and glucagon on systolic properties of the normal and septic isolated rat heart

Abstract

Controversy exists in the literature concerning the effects of insulin and glucagon on cardiac muscle contractility, in particular during anoxia, ischemia or sepsis. The purpose of the present study was to determine the effects of insulin and glucagon on the systolic function of the normal and the dysfunctioning septic rat myocardium in the Langendorff preparation. In the normal isolated rat heart, neither insulin nor glucagon exhibited any lasting inotropic effect on systolic function or coronary flow. Sepsis (cecal ligation and puncture) resulted in a dramatic reduction of systolic function to 44% of control animals. All insulin-containing formulations tested improved systolic function in septic hearts by a mean of 85% compared to Krebs and glucose only. However, this improvement did not reach statistical significance compared to the use of Krebs and glucose only. Glucagon at 100 micrograms/l was doing as well as Krebs and glucose alone while at 1 mg/l glucagon was only able to maintain pre-perfusion contractility. Our results suggest that neither insulin nor glucagon seem to possess special inotropic properties for the isolated perfused normal or septic rat heart.

Insulin-like growth factors and insulin increase the contractility of neonatal rat cardiocytes in vitro

“…This is in accordance with insulin's inotropic effect on the heart in vivo (12,25) or in the perfused heart system (17,28). Specific insulin receptors displaying high affinity binding could be detected on rat cardiocytes in culture (8) and acute metabolic effects in vitro could be elicited by physiological insulin concentrations (12).…”

“…The influence of insulin on the postnatal heart in vivo and on isolated postnatal myocardial cells has been the subject of various investigations. However, all reported effects were observed after the administration of pharmacological (1 ttg to 10 mg) doses of insulin (12,16,17,24,25,28). In dogs the left ventricular function improved significantly after injection of high doses of insulin during experimental, ischemic heart failure by coronary embolization (25), or after termination of extracorporal circulation when repeated, high doses of insulin were given prior to cooling and cardioplegia (12).…”

“…In dogs the left ventricular function improved significantly after injection of high doses of insulin during experimental, ischemic heart failure by coronary embolization (25), or after termination of extracorporal circulation when repeated, high doses of insulin were given prior to cooling and cardioplegia (12). High doses of insulin showed positive inotropic effects in the isolated rat heart (17,28) and papillary band of cats (16). Generally, the effects of insulin under these experimental conditions were observed 10-20 min after its application and therefore are probably secondary to an improvement of the energy state of the myocardial cell via enhanced glucose and lipid metabolism (3).…”

The effect of insulin on the heart

“…23 However, others have not been able to reproduce these results. 13,[24][25][26][27] These conflicting results may be due to the already normal function of myocardium, in which it is more difficult to enhance myocardial function than in already dysfunctional myocardium, e.g. dysfunction caused by ischaemia.…”

Insulin Causes [Ca 2+ ] i -Dependent and [Ca 2+ ] i -Independent Positive Inotropic Effects in Failing Human Myocardium

“…1 Insulin, a polypeptide of 51 amino acids, is known to regulate serum glucose levels, protein synthesis, and growth. Effects of insulin on myocardial function have been tested in several animal models under in vitro and in vivo conditions, and controversial results with both enhanced contractility and myocardial performance [2][3][4][5][6] or no functional effects 7,8 have been reported. Insulin infusions improved ventricular function in one study in humans 9 but had no effect in another.…”