ABSTRACT
Address Correspondence to: Morris F.White, Ph.D., Howard Hughes Medical Institute, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215. Tel: (617) 732-2578; fax: (617) 732-2593; Email: morris.white@joslin.harvard.edu
INTRODUCTION
The appropriate storage and release of energy during states of feeding and fasting is essential for survival and is generally controlled by the action of insulin (1). Insulin is secreted by the β cells in the pancreatic islets of Langerhans in response to elevated blood glucose or certain amino acids during and following a meal. Insulin promotes the storage of glucose as glycogen in the liver and muscle, the storage of amino acids in muscle proteins, and the accumulation of triglycerides in adipose tissue (Figure 1). Diabetes mellitus occurs when insulin fails to perform its physiological function, owing either to an absolute lack of insulin (Type 1), or to a relative insulin insufficiency owing to peripheral insulin resistance (Type 2) (1). Although insulin was discovered over 75 years ago, the molecular mechanisms by which insulin acts are only now being revealed through a multidisciplinary approach including genetics, biochemistry, cell and molecular biology (2, 3). Recently, the use of transgenic mice is beginning to reveal novel relations between insulin/IGF-1 signaling transduction cascades and metabolic regulation. This new information might provide a molecular basis to develop rational treatments for type 1 and type 2 diabetes.
