Insulin receptor half-life

Glucagon is extensively degraded in the liver and kidney as well as in plasma and at its tissue receptor sites. Because of its rapid inactivation by plasma, chilling of the collecting tubes and addition of inhibitors of proteolytic enzymes are necessary when samples of blood are collected for immunoassay of circulating glucagon. Its half-life in plasma is between 3 and 6 minutes, which is similar to that of insulin. 

The insulin receptor is synthesized as a preproreceptor of 1370 amino acids. The proreceptor (molecular mass 190 kDa on SDS-PAGE) is glycosylated (Kahn, 1985) in the Golgi region, proteolytically cleaved into mature a- and /3-subunits, and inserted in the plasma membrane (Fehlmann et al., 1982) or degraded. The half-life of the insulin receptor was determined to be 7-12 hours (Kahn, 1985). 

There are two direct consequences of insulin binding to the receptor. First the tyrosine kinase activity on the / -subunit is activated. This causes autophosphorylation and also phosphorylation of intracellular proteins. Although a number of proteins have been phosphorylated in vitro, it is not yet clear what is the normal physiological substrate or substrates. In mammals, several cellular protein substrates have been proposed, but the precise role of any of the proteins is unclear. A 70 kDa protein has been proposed as a substrate in cultured foetal chick neurons, and a 72 kDa phosphoprotein in domestic fowl hepatoma, but the functions of these polypeptides are unclear (Simon Taouis, 1993). Second, binding causes internalisation of the receptor, after which the insulin is removed and degraded in the lysosomes and the receptor recycled back to the plasmalemma. In domestic fowl hepatocytes, the half-life of the receptor is about 10 h (Simon, 1989). 

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