Insulin‐induced Enhancement of Uptake of Noradrenaline in Atrial Strips

Abstract

Addition of insulin to the organ bath increased the force of contraction of guinea‐pig left atrial strips driven electrically at 1 Hz The positive inotropic response to insulin remained unaltered in atria depleted of catecholamine or when β‐adrenoceptors were blocked by addition of propranolol to the organ bath The response of isolated atria to noradrenaline was significantly reduced in the presence of insulin Insulin affected neither the calcium accumulating abilities of the heart sarcolemma, mitochondria or microsomes, nor the cyclic adenosine 3′, 5′‐monophosphate (cyclic‐AMP)‐protein kinase‐induced stimulation of microsomal calcium uptake Addition of insulin to the organ bath enhanced significantly the ability of the cardiac tissue to take up [3H]‐noradrenaline as well as [3H]‐metaraminol. The activities of monoamine oxidase and catechol‐O‐methyl transferase were not changed after addition of insulin to homogenates of the heart The ability of insulin to facilitate uptake of noradrenaline would be expected to cause a decrease in the amount of the amine reaching the receptors, thus leading to a diminished response to this amine. This may explain, at least in part, insulin‐induced subsensitivity to noradrenaline This view is supported by the observation that after blockade of amine uptake by destruction of nerve terminals, insulin failed to reduce the positive inotropic response to noradrenaline.

Exogenous insulin augments in healthy volunteers the cardiovascular reactivity to noradrenaline but not to angiotensin II.

“…Furthermore, studies in vitro and in animals suggest that insulin has chronotropic and inotropic properties itself, but that this action does not dependent on changes in catecholamines (36,37). Whether the observation of an increased ability of tissues to take up NA after insulin administration bears any relation with the observed increase in the plasma clearance of NA in our study, is unclear.…”

“…Several in vitro studies suggest, however, that insulin may in fact attenuate the vascular responsiveness to NA (10,35), possibly by enhancing the ability of tissue to take up NA (36). Furthermore, studies in vitro and in animals suggest that insulin has chronotropic and inotropic properties itself, but that this action does not dependent on changes in catecholamines (36,37).…”

Acute effects of insulin on cardiovascular function and noradrenaline uptake and release

“…Several authors have shown in animal studies and in isolated preparations that insulin increases cardiac muscle contraction, an effect which is not dependent on glucose or catecholamines [3][4][5]. Page et al [6] showed that insulin increased heart rate in diabetic patients with normal cardiovascular reflexes while Jacobsen and Christensen [7] observed that the tachycardia induced by insulin in rabbits was not inhibited by autonomic nervous blockade.…”

“…Insulin may act directly on peripheral nerve terminals. Bhagat et al [5] noted that insulin induced antagonism to NA by enhancing the ability of the tissues to take-up NA. Such a mechanism might explain the hypotensive effect of insulin in sympathectomized patients because plasma NA does not increase after insulin administration in these patients; this abnormality may result in an attenuated vasoconstrictor activity.…”

“…Several authors have shown that insulin impairs the inotropic action of NA on the heart [4,5]. Furthermore, insulin may induce a fall in arterial pressure in sympathectomized patients [18][19][20][21].…”