INSULIN 2ND-MESSENGERS

The molecular pathways for insulin's signal transduction from its cell surface receptor to the cell's interior metabolic machinery remain in many ways uncharted. Lately two molecules have been proposed as secon d messengers transducing the insulin signal into the target cell. One is a phosphooligosaccharide/inositolphosphoglycan and the other is dia cylglycerol, both deriving from the same plasma membrane glycolipid, w hich is hydrolysed in response to insulin treatment. The phospho-oligo saccharide appears to mediate many metabolic effects of insulin throug h control of the phosphorylation state of key regulatory metabolic enz ymes. Diacylglycerol may mediate insulin's stimulation of glucose tran sport over the plasma membrane. The glycolipid precursor of these puta tive second messengers, as well as the receptor for insulin, appear to be localized in caveolae microdomains of the plasma membrane, and glu cose transporters accumulate in caveolae in response to insulin treatm ent, suggesting a focal role for caveolae in insulin signalling.