Insulin worms its way into the spotlight

Obesity and the occurrence of diabetes are on the rise. Much of this is attributable to a more sedentary lifestyle and high caloric intake in industrialized countries and is a major cause of a variety of health problems. Obesity and diabetes are intimately linked to insulin, which increases glucose uptake in cells and serves as a primary regulator of blood glucose levels. Insulin has been an important target of investigation for decades, as indicated by its sequence determination by Sanger and colleagues in 1955 (Brown et al. 1955; Ryle et al. 1955; Murray-Rust et al. 1992), and is now the subject of renewed interest.

In addition to its role in glucose homeostasis (Saltiel and Kahn 2001), studies in the last several years have revealed a central role of insulin signaling in life span and aging in Caenorhabditis elegans. This surprising finding has allowed researchers to gain a foothold on a difficult, but important, biological problem. The control of life span by insulin signaling is not restricted to C. elegans, but now has been extended to equivalent pathways inDrosophila and mammals.

Because of these important roles in growth, development, and aging, insulin signaling is receiving scrutiny from scientists in diverse fields. Many downstream signaling components have now been identified and examined for their participation in metabolism and aging. Since the complete sequence of many organisms is now available, the identification of ligands has become easier and has revealed unexpected complexity. Sorting out the functions of these ligands will be an important aspect toward gaining a more complete understanding this signaling pathway. In this issue of Genes & Development, two papers (Hua et al. 2003; Li et al. 2003) address the structural and biological activities of some of these newly identified ligands. Ruvkun and colleagues …