Editorial
Authors: Subodh Verma, Aaron S. Dumont, John H. McNeill
 *
Journal: Cardiovascular Research (1999)

Resistance to the metabolic effects of insulin (insulin infarction, valvular disease and cardiomyopathy [9]. Left resistance) and hyperinsulinemia have been suggested to ventricular hypertrophy (LVH) is a strong predictor of contribute to a cluster of abnormalities including diabetes, cardiovascular morbidity and mortality independent of hypertension, obesity, hyperlipidemia, atherosclerosis, corfactors such as hypertension or obesity [10]. The recognionary artery disease and polycystic ovary syndrome [1–3]. tion that LVH as one of the most important predictors of Although the causality of this link is still debated, pharmaadverse cardiovascular outcomes, has led to a surge of cological studies demonstrating the ability of insulin-enresearch efforts aimed at understanding the biochemical, hancing agents to counter these conditions [1,3,4] suggest hemodynamic and genetic basis of LVH and exploring that insulin resistance and hyperinsulinemia may play a therapeutic strategies geared towards abrogating LVH. It is central role in the development and course of these clear that the final expression of LVH may involve a diseases. Of importance, in this regard, is the increasing complex inter-play between mechanical, neural, hormonal, awareness that insulin, over and above its well known metabolic and genetic factors [9,11,12]. As elegantly effects on carbohydrate, protein and lipid metabolism, described by Homcy [11], the molecular signals underlying exerts distinct cardiac, vascular and sympathetic responses the development of cardiac hypertrophy involve multiple [2,5]. This has led to the suggestion that changes in the signal switches to a multiple set of wires and an enormous these actions of insulin (in states of insulin resistance) may cross talk amongst each. The existence of the final be important in modulating the final expression of both common element that integrates these extracellular and cardiovascular and metabolic diseases. For example, resistintracellular events and leads to hypertrophy remains ance to the vasodilatory action of insulin (vascular insulin unknown. resistance) has been documented in the insulin resistant The purpose of this editorial is to highlight another states of diabetes, obesity and hypertension [6–8]. Vascular interesting facet of cardiac hypertrophy as highlighted by insulin resistance may sensitize /predispose the vasculature the work of Paternostro et al. [13] in this volume of to the effects of pressors and lead to increased vascular Cardiovascular Research. The authors uncover, for the smooth muscle tone and reactivity [5,8]. As the vasodilatfirst time, the presence of myocardial insulin resistance in ory actions of insulin contribute significantly to whole patients with cardiac hypertrophy independent of changes body glucose disposal [5], vasoconstriction (secondary to in myocardial blood flow and predisposing conditions such vascular insulin resistance) may play a role in the developas hypertension, diabetes and coronary artery disease. In ment or reinforcement of skeletal muscle /whole body their study, myocardial glucose uptake (MGU) was cominsulin resistance. pared between normotensive and non-diabetic patients with Cardiac hypertrophy represents the response of the heart cardiac hypertrophy (secondary to aortic stenosis) vs. to overload secondary to conditions such as hypertension, controls using PET and 2-deoxy-D-glucose uptake. In the presence of euglycemic hyperinsulinemia, a marked reduction in MGU was reported in the cardiac hypertrophy group when compared to the control group (0.4860.02 vs. 0.7060.03 mmol /min/g, P,0.01). The inability of similar insulin concentrations to evoke comparable changes in *Corresponding author. Tel.: 11-604-822-9373; fax: 11-604-822MGU clearly suggests the presence of cardiac insulin 8001. resistance in the subset of patients with cardiac hyperE-mail address: jmcneill@unixg.ubc.ca (J.H. McNeill) See pages 246–253. trophy. To examine the contribution of altered glucose