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

Abstract

Aims/hypothesis. We investigated the effect of physiological hyperinsulinaemia on global and regional myocardial blood flow and glucose uptake in five patients with Type II (non-insulin-dependent) diabetes mellitus and seven healthy control subjects. Methods. Myocardial blood flow was assessed by positron emission tomography with oxygen-15 labelled water (H 2 15 O) either before or after 1 h of euglycaemic hyperinsulinaemia. Myocardial glucose uptake was assessed by positron emission tomography and fluorine-18 labelled fluorodeoxyglucose ( 18 FDG). Results. During hyperinsulinaemia, myocardial blood flow increased from 0.91±0.03 to 1.00±0.03 ml . min -1 . g -1 in control subjects (p<0.005) and from 0.81±0.02 to 0.95±0.04 ml . min -1. g -1 in diabetic patients (p<0.0005). Corresponding glucose uptakes were 0.56±0.01 and 0.36±0.02 µmol . min -1. g -1 (p<0.0001), respectively. During hyperinsulinaemia, the regional distribution of myocardial blood flow and glucose uptake showed higher values in the septum and anterolateral wall (short axis) and in the mid-ventricle (long axis) in control subjects, and insulin action was circumscribed to these regions. In diabetic patients, the regional distribution of glucose uptake was similar; however, insulin-induced increase of myocardial blood flow was mainly directed to the postero-inferior areas (short axis) and to the base (long axis) of the heart, thus cancelling the predominance of the anterior wall observed before insulin administration. Conclusion/interpretation. These results provide evidence that insulin-mediated regulation of global myocardial blood flow is preserved in Type II diabetic patients. In contrast, the regional re-distribution of myocardial blood flow induced by insulin is directed to different target areas when compared with healthy subjects, thereby resulting in a mismatch between blood flow and glucose metabolism. [Diabetologia (2002[Diabetologia ( ) 45:1404[Diabetologia ( -1409 Keywords Insulin, diabetes, myocardial glucose metabolism, myocardial perfusion, positron emission tomography. The availability of non-invasive quantification of myocardial blood flow (MBF) with positron emission tomography (PET) has re-opened the long debated issue concerning the role of insulin in the regulation of myocardial perfusion. A better understanding of this issue carries important pathophysiological implications on the relation between insulin resistance and enhanced cardiovascular risk. 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

The Vasculature in Prediabetes

“…Insulin vasodilates skeletal muscle 6, 37 and coronary 38, 39 vasculature. Insulin resistance contributes to endothelial dysfunction in prediabetes (Figure 1).…”

Insulin-Stimulated Myocardial Glucose Uptake and the Relation to Perfusion and the Nitric Oxide System

“…Since recent studies using positron emission tomography (PET) [6, 7], in contrast to previous studies using coronary sinus catheterization, have demonstrated an increase in myocardial perfusion following insulin administration, we hypothesized that this mechanism is an inherent component of insulin-stimulated MGU. The aim of the present investigation was to study the influence of high physiologic insulinemia on myocardial perfusion and glucose uptake and the involvement of EDNO in healthy volunteers.…”

“…Two recent studies have shown a slight vasodilation in the myocardium following local coronary [21]and systemic insulin infusion [6]in patients with coronary artery disease and type 2 diabetes, respectively. Our finding is in accordance with the majority of studies whether coronary sinus flow measurement or PET was used [3, 4, 7].…”

Run for your life: can exercise be used to effectively target GLUT4 in diabetic cardiac disease?

“…This is generally demonstrated using positron emission tomography imaging of a radiolabelled glucose analogue that is infused during a euglycemic-hyperinsulinemic clamp. This reduction in cardiac glucose uptake has been demonstrated independent of any limitation in cardiac blood flow, although there is evidence that relative regional perfusion may be altered ( Iozzo et al, 2002b ). Reduced glucose uptake could have significant consequences for cardiac metabolism and therefore performance due to the aforementioned rapid flux and oxygen efficient generation of ATP via glucose metabolism, particularly in the presence of subclinical cardiovascular stress (likely in patients with diabetes).…”