ABSTRACT
Address correspondence to: Robert V.Farese, M.D., J.A.Haley Veterans’ Hospital Research Service, and Department of Internal Medicine, University of South Florida College of Medicine 13000 Bruce B.Downs Blvd., (VAR 151) (813)972-7662 Fax (813) 972-7623 Email: rfarese@com1.med.usf.edu
FOREWORD
From a clinical viewpoint, the regulatory effect of insulin on glucose homeostasis is unsurpassed in importance in the field of Endocrinology. In particular, the regulation of glucose transport by insulin is of utmost importance in controlling glucose uptake and subsequent storage in muscle and adipose tissues, and derangements in glucose uptake figure prominently in the pathogenesis, not only of acquired forms of insulin resistance, but also of the initial (presumably genetic) defect in insulin action that precedes the appearance of glucose intolerance and overt type II diabetes mellitus. Needless to say, the cause of this initial defect in glucose transport is still uncertain. On the other hand, during the past few years, we have gained considerable insight into intracellular signaling factors that appear to play instrumental roles in regulating glucose transport. In particular, it now appears that phosphatidylinositol (PI) 3-kinase (3K) is required, at least partly, for insulin effects on both glucose transport and subsequent storage of glucose in glycogen. Moreover, recent findings suggest that atypical protein kinase C (PKC) isoforms, ζ and λ, and, perhaps, protein kinase B (PKB or Akt), serve as downstream effectors for PI3K in controlling the rate-limiting step in glucose transport, viz., the translocation of GLUT4 glucose transporters from the endoplasmic reticulum to the plasma membrane. The latter process is very complex and most likely requires the integrated input from many signaling factors. Indeed, many of the pieces of the puzzle appear to be falling into place, and it is probably only a matter of time before we largely understand how insulin regulates glucose transport, and ultimately identify the causes for acquired and genetic forms of insulin resistance.
