The biological activity of structurally defined inositol glycans

Abstract

BACKGROUND: The inositol glycans (IGs) are glycolipid-derived carbohydrates produced by insulin-sensitive cells in response to insulin treatment. IGs exhibit an array of insulin-like activities including stimulation of lipogenesis, glucose transport and glycogen synthesis, suggesting that they may be involved in insulin signal transduction. However, because the natural IGs are structurally heterogeneous and difficult to purify to homogeneity, an understanding of the relationship between structure and biological activity has relied principally on synthetic IGs of defined structure. DISCUSSION: This article briefly describes what is known about the role of IGs in signal transduction and reviews the specific biological activities of the structurally defined IGs synthesized and tested to date. CONCLUSION: A pharmacophore for IG activity begins to emerge from the reviewed data and the structural elements necessary for activity are summarized.

Figure 1. Insulin signal transduction

Inactive proteins are indicated by a paler color. Protein shape and color depend on the protein function: kinases (and insulin receptor substrates) are green and rectangular with rounded edges. Regulatory domains (e.g., the p85 domain of PI3 kinase) and adaptor proteins are light blue and oval. Phosphatases are dark blue and rectangular. Lyases and synthases are brown. Blue arrows denote a chemical transformation (e.g., PIP2→PIP3) as well as movement of proteins. Black arrows point to the protein target. A solid arrow indicates that the reaction has been established. Dashed arrows refer to pathways that are not yet well established.

Figure 2. Mechanism of inositol glycan (inositolphosphate glycan) action on cell surfaces

GPI: Glycosylphosphatidylinositol; IPG: Inositolphosphate glycan. From [34,35].