Transcappilary Glucose Exchange in Muscle and Adipose Tissue

In recent years, the interstitial fluid (ISF) of peripheral tissues (e.g., adipose tissue) has received considerable attention as an alternative site for the measurement of glucose concentrations. Various methods, such as microdialysis, open-flow microperfusion and electrochemical sensors, have been proposed for the assessment of glucose in the ISF rather than blood. The ISF glucose values obtained by such methods may be used to estimate blood glucose levels. In this way, the ISF-based glucose assessment could potentially replace the more invasive blood glucose measurements. Hence, ISF-based glucose measuring methods could substantially improve the lives of people with diabetes. The relationship between blood and ISF glucose levels has been shown to be determined by a number of factors. The main factor, however, seems to be the ability of a tissue to exchange glucose across the capillary walls. In a given tissue, this factor may largely determine the magnitude of the blood to ISF glucose differences under daily life conditions. There have been few attempts to assess the transcapillary glucose exchange properties of the peripheral tissues of the rat, dog and sheep. In these previous animal studies, glucose kinetics simultaneously observed in blood and ISF have been mathematically treated to yield quantitative information on the tissue-specific ability to exchange glucose across the capillary walls. To the best of our knowledge, similar evaluations of transcapillary glucose exchange in peripheral tissues in humans have not been carried out. Therefore, the aim of the present research project is to quantify the kinetics of the exchange of glucose between the plasma and the ISF of human skeletal muscle and adipose tissue under fasting conditions. To achieve this, we will simultaneously sample blood and ISF of muscle and adipose tissue during intravenous infusions of small amounts of metabolizable and nonmetabolizable sugars in fasted non-obese humans. The sampling of the ISF from the two tissues will be accomplished by employing the open-flow microperfusion technique. The observed glucose kinetics in blood and ISF will then be analyzed by a mathematical model to yield kinetic parameters describing transcapillary glucose exchange in human skeletal muscle and adipose tissue. The quantitative information on the transcapillary glucose exchange properties in these tissues obtained by the proposed investigations will be used to improve the ISF-derived estimation of blood glucose concentrations.

In a given tissue, the relationship between blood glucose and the glucose in the interstitial fluid (ISF) is mainly determined by the ability of the tissue to exchange glucose across the blood vessel walls. In our project supported by the Austrian Science Fund, we have devised an experimental procedure for the quantitative assessment of glucose exchange across blood vessel walls in human skeletal muscle and adipose tissue. As a first step, we have applied this experimental procedure in normal humans under fasting conditions. We found that the ability to exchange glucose across the capillary walls is similar in skeletal muscle and adipose tissue under fasting conditions. The devised experimental procedure and the results of its first application in normal humans have been described in detail in our recent article published in the American Journal of Physiology (AJP 285: E241-51, 2003). In a follow-up project, we wish to apply the devised experimental procedure in diabetic patients. The results of these studies may offer important insight into the relationship between blood and interstitial glucose concentration in skeletal muscle and adipose tissue of diabetic patients. Quantitative information on the relationship between blood and ISF glucose levels in such tissues is a prerequisite for the application of ISF-based glucose measuring methods. These methods could replace the more invasive blood glucose measurements, and, thereby, substantially improve the lives of people with diabetes.