Insulin resistance and the disruption of Glut4 trafficking in skeletal muscle

This is the authors' abstract. We don't add key points for this paper.

The facilitative transport of glucose across animal cell membranes is mediated by members of the Glut protein family (1). These 50- to 60-kDa glycoproteins are ubiquitously expressed in mammalian tissues and are responsible for the uptake of sugar from the blood into cells, supplying cellular glucose for ATP production and for a wide variety of anabolic reactions. Additionally, glucose transport in certain tissues plays a critical role in whole-body glucose homeostasis. During fasting or starvation, the liver and kidney maintain euglycemia by becoming net producers of blood glucose, initially via the breakdown of glycogen stores and later through the catabolism of amino acids. Conversely, when the insulin level rises during the postprandial period in response to ingested carbohydrates, fat and muscle tissue become the major sites of glucose metabolism and storage. The appropriate output or uptake of glucose from these tissues via the Glut proteins is critical to health and survival. For example, a disruption in the normal process by which insulin stimulates glucose transport into skeletal muscle is the cause of the peripheral insulin resistance associated with non–insulin-dependent diabetes mellitus (NIDDM) (2). Insulin resistance is the earliest detectable abnormality observed during the natural history of NIDDM and is believed to be a major triggering event in the development of the disease (3). Thus, a detailed understanding of how insulin regulates glucose transport in muscle is essential to unraveling the molecular basis of NIDDM. In this issue, Yang et al. (4) identify syntaxin 4 as one of the key molecular components in insulin-stimulated glucose transport in skeletal muscle. They also provide evidence supporting a novel mechanism for the pathogenesis of insulin resistance — the downregulation of a factor involved in glucose transporter subcellular trafficking.