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DIABETES, VOLUME 45, AUPPLEMENT 1, JANUARY 1996, PAGES S1-S13

Introduction

Erik J. Henriksen, Guenther J. Dietze, and Werner Muller-Esterl, Editors

According to the classic work of the renowned diabetologist Elliott P. Joslin, dynamic endurance exercise, in addition to diet and insulin, is one of the most important therapeutic intervenions for treating diabetes. For this reason, the study of the regulation of substrate utilization during muscular exercise has always been of great scientific importance. Since 1887, when Chaveau and Kaufmann first discovered that muscle contraction is accompanied by an increase in blood flow and he uptake of oxygen and glucose, there have been innumerble in vivo and in vitro studies examining this phenomenon. These studies have demonstrated that contracting muscle undergoes a number of adaptive responses that supply the tissue with sufficient oxygen and substrates to meet the increased energy demand of the working muscle cells. Similarly, numerous in vivo and in vitro studies have shown that these same adaptive responses occur in the heart during physical exercise to match oxygen and substrate supply with the increased metabolic demand of the myocardium.

One of the long-standing goals of muscle biologists is to identify the molecular mechanisms underlying the communication between contracting muscle and the neighboring vascular beds that results in a local vasodilation and increased oxygen and substrate delivery. To date, however, this issue remains unclear.

This phenomenon of the metabolic responses of muscle during exercise has been the subject of previous supplements to Diabetes, the most recent appearing in 1978. In the intervening years, much new experimental information related to this topic has accumulated. Therefore it is now appropriate to continue this journal's tradition of providing cutting-edge scientific information with a supplement presenting some of the more recent experimental results on the regulation of skeletal and cardiac muscle metabolism by insulin and contractions.

New experimental methodologies and approaches have underscored the advances made in the area of muscle metabolism regulation. For example, nuclear magnetic resonance (NMR) spectroscopy has allowed the noninvasive in vivo determination of rapid changes in the cytosolic concentrations of ATP, ADP, creatine phosphate, Pi, and H+ in human muscle cells during exercise. In addition, in vivo investigations, as well as studies using isolated endothelial cell systems, have demonstrated that the vascular endothelium can be considered an endocrine apparatus, replete with receptors for locally produced molecules. The bound receptors can activate an intracellular cascade of enzyme systems, which eventually lead to the release into the blood of vasodilatory effectors that help to facilitate an increase in substrate supply to the underlying muscle tissue.

Bradykinin (BK) can be included now in the list of recognized substances, including adenosine, that have specific endothelial receptors and, on the basis of their molecular characteristics, can be considered potential physiological mediators. Endothelium-derived nitric oxide (EDNO) is a substance that is created as a result of a multienzyme cascade in endothelial cells and that can cause marked vasodilation. The production of EDNO is increased in a dose-dependent manner through BK action on endothelial cells. Of considerable interest are recent studies in the human forearm demonstrating that one possible mechanism of insulin action in increasing muscle glucose disposal is an EDNO-mediated vasodilation.

To bring these new scientific findings into perspective and to spark discussion of future directions in integrative regulation of skeletal muscle and myocardial glucose metabolism through hormonal and contractile stimuli, we invited experts in various fields to participate as both speakers and discussants in an international symposium. This symposium took place on September 3 and 4, 1994, in the Buhlerhohe, an idyllic setting in the Black Forest in southwestern Germany. The following provides an overview of the various articles included in this supplement.

Last updated: 5/30/96
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