Tracer studies of in vivo insulin action and glucose metabolism in individual peripheral tissues.

The ability to study in vivo insulin action in specific muscle types and other individual tissues has been considerably enhanced following adaptation of the euglycemic clamp technique to the rat. The importance of this model derives particularly from its combination with administration of 3H-2-deoxyglucose and 14C-glucose. Analysis of the metabolic fate of these tracers at the conclusion of the clamp enables an assessment to be made of insulin action at both the whole body and the individual tissue level, the latter by estimating a tissue-specific glucose metabolic rate (from 3H-2-deoxyglucose phosphorylation). Information on stored vs utilised glucose can be obtained by simultaneously estimating 14C-glucose incorporation into glycogen and/or lipids. This review briefly considers the basis of the technique and its recent application. It has been used to demonstrate in the rat that in vivo insulin sensitivity differs widely among insulin target tissues, such as adipose tissue, red and white skeletal muscle, and cardiac muscle. The technique has provided a means to study how factors such as diet, exercise, pregnancy, stress hormones and pharmacological agents modify in vivo insulin action in muscle and other tissues, to compare insulin and exercise as stimuli to muscle glucose uptake, and to examine factors which might be important in the aetiology of muscle insulin resistance. These new tracer techniques for in vivo use with the glucose clamp have narrowed the gap that exists between established whole body and cellular in vitro approaches to the study of insulin action and glucose metabolism.