Regional myocardial blood flow and glucose utilization during fasting and physiological hyperinsulinemia in humans

Abstract

We investigated the effect of insulin on total and regional myocardial blood flow (MBF) and glucose uptake (MGU) in healthy subjects (50 +/- 5 yr) by means of positron emission tomography (PET) with oxygen-15-labeled water (H(2)(15)O) and fluorine-18 labeled fluorodeoxyglucose ((18)FDG) before and during physiological hyperinsulinemia (40 mU.min(-1).m(-2)). Twelve male subjects were included in the study. During hyperinsulinemia, MBF increased from 0.91 +/- 0.28 to 1.01 +/- 0.31 ml.min(-1).g(-1) (n = 7 patients, P = 0.05; n = 112 regions, P < 0.005). Intersubject variability ranged from -3.0 to +41%. MGU increased from 0.11 +/- 0.08 (n = 5) to 0.56 +/- 0.08 micromol.min(-1).g(-1) (P < 0.0001, n = 7). MBF and insulin-mediated MGU were higher in the septum and anterior and lateral wall along short-axis regions of the heart. During hyperinsulinemia, MBF was also higher in the apex and midventricle compared with the base. MBF and MGU were positively correlated before (r = 0.66, P < 0.0001) and during hyperinsulinemia (r = 0.24, P < 0.05). These results provide evidence that insulin stimulates MBF in normal human hearts and appears to involve mainly those regions of the heart where insulin-mediated MGU is higher. Furthermore, regional distribution of insulin-stimulated MBF and MGU does not appear to be uniform across the left ventricular wall of healthy subjects.

Similar patterns of myocardial metabolism and perfusion in patients with type 2 diabetes and heart disease of ischaemic and non-ischaemic origin

“…The ability of an acute insulin infusion to induce an increase in myocardial blood flow has been previously reported in healthy individuals as well as in type 2 diabetic patients with and without CAD [14,24,25]. We now describe a similar effect in patients with type 2 diabetes and non-ischaemic HF.…”

Mismatch between insulin-mediated glucose uptake and blood flow in the heart of patients with Type II diabetes

“…As previously shown in healthy people [7], this effect was not uniformly distributed across myocardial regions in either of the two groups. Although the magnitude of change followed the heterogeneous metabolic requirements observed across myocardial regions in the control group, the two functions appeared to lack such coordination in diabetic patients.…”

“…Whereas methodological diversities might explain some previously reported discrepancies, more recent studies are consistent in supporting a vaso-active effect of insulin in the whole myocardium [7,8,9]. Based on the recent study showing that in healthy subjects physiological hyperinsulinaemia potentiates the coronary vasodilatation induced by maximal adenosine stimulation, the term insulin-mediated 'coronary flow reserve' can be introduced [8].…”

“…In previous studies [1,2,3,4,5,6], the use of invasive techniques and/or anaesthesia could have introduced confounding factors, such as variable degrees of sympathetic activation and circulating NEFA concentrations. Using PET and oxygen-15 labelled water, we have shown that in healthy humans a small increase in resting myocardial perfusion occurs early during insulin stimulation [7], and that the magnitude of this change seems to be larger in those segments of the heart with higher glucose consumption. It has been reported [8] that physiological hyperinsulinaemia amplifies adenosine-induced hyperaemia in healthy men.…”

Cardioprotective Effects of Insulin

“…90 In humans, insulin increased coronary sinus and myocardial blood flow and reduced coronary resistance. [91][92][93] Insulin-induced coronary vasodilation is related to NO production. 94 Insulin facilitates endothelial production of NO by upregulating the expression of eNOS via the PI3K-Akt pathway, without inducing inducible NO synthase.…”