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

Abstract

Insulin induces a broad spectrum of effects over a wide time interval. It also stimulates the phosphorylation of some cellular proteins, while decreasing 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 cascade initiated by the tyrosine kinase activity of the insulin receptor followed by involvement of different MAP-kinases. Another pathway suggests the existence of low molecular weight insulin mediators whose synthesis and/or release is initiated by insulin. Comparable analysis of two kinds of insulin mediators, namely inositolphosphoglycans and prostaglandylinositol cyclic phosphate (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 various monkey tissues before and twice during an euglycemic hyperinsulinemic clamp have been presented. It has been concluded that in vivo insulin increases 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-induced insulin resistance and diabetic embryopathy. Further studies on cPIP and other types of insulin mediators are necessary to aid our understanding of insulin action.

Insulin-Mimicking Bioactivities of Acylated Inositol Glycans in Several Mouse Models of Diabetes with or without Obesity

“…Glycogen content was determined by the phenol-sulfuric acid spectrophotometric method at 490 nm [13] and expressed as micrograms of glycogen per milligram of liver.…”

Prostaglandylinositol cyclic phosphate, the natural antagonist of cyclic AMP

“…It was isolated from mini‐pig livers and from brewer's yeast 5 . Cyclic PIP synthesis was characterized in livers of rhesus monkeys 12 . and in Dictyostelium discoideum 13 .…”

“…5 Cyclic PIP synthesis was characterized in livers of rhesus monkeys. 12 and in Dictyostelium discoideum. 13 The synthesis of cyclic PIP increases with increasing concentration of hormones that stimulate its synthesis.…”

Synthesis of Differentially Protectedmyo- andchiro-Inositols fromd-Xylose: Stereoselectivity in Intramolecular SmI2-Promoted Pinacol Reactions

“…Natural phosphorylated and/or glycosylated inositols have been found to play central roles in a variety of cellsignaling pathways in animals, [1][2][3][4][5][6][7][8][9] in desiccation tolerance in plants, [10][11][12][13][14][15] and as protein anchors in all eukaryotes. 16,17 These diverse, and in some cases medically useful, activities have stimulated great interest in the synthesis of these compounds and their analogues.…”