Exercise and insulin increase muscle fatty acid uptake by recruiting putative fatty acid transporters to the sarcolemma.

Skeletal muscle metabolic energy, needed to maintain contractile activity, is mainly obtained from glucose and long-chain fatty acids. Recent studies have revealed a remarkable parallel between the regulation of uptake of glucose and fatty acids by muscle, in that each is mediated by sarcolemmal transporters that are recruited from an intracellular storage site. The focus of this review is to describe newly obtained insights on the recruitment of fatty acid transporters and their malfunctioning in diabetes. The major fatty acid transporter involved is fatty acid translocase (CD36). Translocation of this protein to the membrane is triggered by muscle contraction and by insulin, and presumably occurs from distinct intracellular pools. This resembles the well documented exercise and insulin-induced recruitment of glucose transporter-4. Whether another transporter, plasma membrane fatty acid-binding protein, is also subject to such recycling is not yet clear. In a rodent model of insulin-dependent (type 1) diabetes, the increased rate of muscle fatty acid uptake could be associated with an increased total amount of fatty acid translocase (CD36). In a model of non-insulin dependent (type 2) diabetes, this increased rate could be associated with a permanent relocalization of fatty acid translocase to the sarcolemma. These findings indicate a pivotal role for the membrane transporter fatty acid translocase in the exercise and insulin-induced increases of muscle fatty acid uptake and utilization, and suggest that malfunctioning of the cellular recycling of fatty acid translocase is involved in the etiology of insulin resistance and type 2 diabetes.