The Membrane Receptor-Non-Adenylate-Cyclase System

So far, it has proven impossible to link any of the physiological actions of insulin to changes in membrane electrical potential (Czech, 1977). It also has not been possible to link changes in monovalent cation concentration to insulin action. The effects of insulin on cellular Na+ and are opposite to those necessary to mimic insulin action insulin causes hyperpolarization and increases intracellular K+ concentration, whereas depolarization and decreased concentration are required to mimic insulin action. 

It has been suggested that insulin releases Ca from the cell membrane and that this Ca + is then the intracellular signal molecule (the third messenger ) which mediates insulin action (Clausen, 1975 Clausen et al., 1974 Kissebah et al., 1975 Fraser, 1975). There is a body of information consistent with this view, but, there also are discrepancies between the action of intracellular Ca + and the physiological action of insulin. Thus, if some of the actions are mediated by the release of calcium from the cell membrane, this does not explain all of the actions of insulin. In the fat cell, calcium appears to promote lipol-ysis, which is contrary to insulin action (Park et al., 1972 Exton et al., 1972 Schimmel, 1976). 

Other possible mechanisms for insulin action have been proposed. It has been proposed that membrane phosphorylation regulates transport activity across membranes. Thus, if membrane phosphorylation decreases transport, it would be expected that dephosphorylation would enhance transport (Randle and Smith, 1958). However, insulin does not appear to phosphorylate plasma membrane proteins (Avruch et al., 1976b,c). The insulin activation of glucose transport in fat cells has been postulated to involve the oxidation of certain membrane sulfhydryl groups to the disulfide form (Czech, 1977). A rat liver plasma membrane subfraction has been isolated containing cAMP phosphodiesterase activity that could be stimulated by nanomolar amounts of 

Growth hormone stimulates growth, protein synthesis, lipolysis, and ketogenesis. The main effect of growth hormone is primarily through the stimulation of amino acid transport. Although theophylline inhibits the effect of growth hormone on amino acid uptake and protein 

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