Prostaglandylinositol cyclic phosphate (cPIP): a novel second messenger ofinsulin action. Comparative analysis of two kinds of 'insulin mediators'

Insulin induces a broad spectrum of effects over a wide time interval. It a lso stimulates the phosphorylation of some cellular proteins, while decreas ing the state of phosphorylation of others. These observations indicate the presence of different, but not necessarily mutually exclusive, pathways of insulin action. One well-known pathway represents a phosphorylation cascad e initiated by the tyrosine kinase activity of the insulin receptor followe d by involvement of different MAP-kinases. Another pathway suggests the exi stence of low molecular weight insulin mediators whose synthesis and/or rel ease is initiated by insulin. Comparable analysis of two kinds of insulin m ediators, namely inositolphosphoglycans and prostaglandylinositol cyclic ph osphate (cPIP), has been carried out. It has been shown that the expression of a number of enzymes, such as phospholipase A(2), phospholipase C, cyclo oxygenase and IRS-1-like enzyme, could regulate the biosynthesis of cPIP in both normal and diabetes-related conditions. Data on the activity of a key enzyme of cPIP biosynthesis termed cPIP synthase (IRS-1-like enzyme) in va rious monkey tissues before and twice during an euglycemic hyperinsulinemic clamp have been presented. it has been concluded that in vivo insulin incr eases cPIP synthase activity in both liver and subcutaneous adipose tissue of lean normal monkeys. It has been also suggested that abnormal production of cPIP could be related to several pathologies including glucocorticoid-i nduced insulin resistance and diabetic embryopathy. Further studies on cPIP and other types of insulin mediators are necessary to aid our understandin g of insulin action. Copyright (C) 2001 John Wiley & Sons, Ltd.