Insulin is the principal regulatory
hormone involved in the tight regulation of fuel metabolism. In response to
blood glucose levels, it is secreted by the beta cells of the pancreas and exerts its effects by binding to
cell surface receptors that are present on virtually all cell types and tissues. In humans, perturbations in
insulin function and/or secretion lead to
diabetes mellitus, a severe disorder primarily characterized by an inability to maintain
blood glucose homeostasis. Furthermore, it is estimated that 90-95% of diabetic patients exhibit resistance to
insulin action. Thus an understanding of
insulin signal transduction and
insulin resistance at the molecular level is crucial to the understanding of the pathogenesis of this disease. The
insulin receptor (IR) is a transmembrane
tyrosine kinase that becomes activated upon
ligand binding. Consequently, the receptor and its downstream substrates become
tyrosine phosphorylated. This activates a series of intracellular signaling cascades which coordinately initiate the appropriate biological response. One important mechanism by which
insulin signaling is regulated involves the
protein tyrosine phosphatases (
PTPs), which may either act on the IR itself and/or its substrates. Two well characterized examples include leuckocyte
antigen related (LAR) and
protein tyrosine phosphatase-1B (PTP-1B). The present review will discuss the current knowledge of these two and other potential
PTPs involved in the
insulin signaling pathway.