During the American Diabetes Association national conference this year in Philadelphia, scientists gathered to discuss recent advances in this field at a session on positive and negative elements in signal transduction. When all was said and done, some puzzle pieces were added, but questions remain.
Because diabetes essentially results from the body's failure to respond to insulin, some researchers are trying to understand the signal transduction pathways that translate the binding of insulin to its receptor into cellular activity changes. The insulin receptor's cytoplasmic portion contains an inherent tyrosine kinase activity that becomes active on extracellular insulin binding, leading to the receptor's autophosphorylation and transphosphorylation of the insulin receptor substrates (IRS-1-3).1 These proteins associate with the regulatory subunit of phosphoinositol-3-kinase (PI3K), activating the enzyme's catalytic subunit, which adds a phosphate group to the 3'-OH position of the inositol ring in inositol phospholipids.
The reaction's products activate 3'-phosphoinositide-dependent kinase (PDK1), which ...
