Traditionally, plasma measurements have been used to monitor metabolic
events and the actions of hormones that are actually taking place wit
hin tissue beds that are anatomically separated from the vascular comp
artment. It is generally assumed that the extracellular fluid (ECF) wi
thin metabolically active tissues is composed of substrates and hormon
es in concentrations that closely approximate those in plasma. Indeed,
this view is implicit in nonsteady-state tracer calculations. However
, through the use of microdialysis techniques in the study of tissue m
etabolism this view is being challenged. Our data suggest that there m
ay be substantial concentration gradients for a variety of fuels betwe
en plasma and ECF, i.e. fuels (e.g. glucose) removed from the circulat
ion being lower and fuels (e.g. glycerol, lactate, some amino acids) p
roduced by tissues being higher than plasma levels. In short, the meta
bolic milieu seen by individual tissues. (and hormone receptors?) may,
at least in some instances, be strikingly different from that in plas
ma, and as a result, plasma measurements by themselves may not appropr
iately define the contributions of specific tissues to metabolic event
s, and overlook the importance of metabolic processes which are largel
y restricted to individual tissue beds. Through the use of microdialys
is as a means of directly sampling ECF from metabolically important bo
dy tissues and with the evolution of its use in animal and human resea
rch, this technique will continue to offer exciting new insights into
tissue metabolism and to investigate fundamental issues that cannot be
addressed by other methods.