Insulin physiologic actions

Processing of GH could go further, with production of relatively small peptides which retain substantial or even enhanced activity, and it has been suggested that this may be important in the actions of the hormone in vivo [131]. In particular, fragments which retain the diabetogenic or insulin-like activities of GH have been reported [95,131]. What role these play in the normal physiological actions of the hormone is unclear. 

Whilst much is known about the physiological actions of insulin and the defects in its synthesis that occur in Type-I diabetes, it is only recently that we have begun to appreciate the nature and properties of the insulin receptor itself. 

Insulin is used for the treatment of Type-I and for Type-II diabetes mellitus, when other therapeutic measures, i.e. appropriate diet and oral antidiabetics, are not sufficient to produce normoglycaemia. The physiological actions of insulin including recent advances in our knowledge on signal transduction have been discussed above (chapter 4). Since treatment of diabetes with insulin attempts only to supplement inadequate insulin secretion, this chapter will concentrate on pharmacokinetics, unwanted effects and clinical applications of insulin and its pharmaceutical preparations. 

The cellular and physiological actions of insulin in the central nervous system. Neurochem. Int. 22 1-10. 

Table 26.1. Physiologic Actions of Insulin and Insulin Counterregulatory Hormones...

A. Physiology Insulin is synthesized as a prohormone, proinsulin, an 86-amino-acid singlechain polypeptide. Cleavage of proinsulin and cross-linking result in the two-chain 51-peptide insulin molecule and a 31-amino-acid residual C-peptide. Neither proinsulin nor C-peptide appear to have any physiologic actions. 

Woznitik, M., Rydzewski, B., Baker, S.P. and Raizada, M.K. 1993. The cellular and physiological actions of insulin in the central nervous system. Neurochem. Int. 22 1-10 Xiao, J., Perry, G., Tioncoso, J. and Monteiro, M.J. 1996. a-Calcium-calmoduhn-dependent kinase II is associated with paired helical filaments of Alzheimer s disease. 1. NeuropathoL Exp. Neurol. 55 954-963... 

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). 

I have already mentioned leptin. There are several others, notably including adiponectin, a protein present in high concentrations in blood. Adiponectin is an antihyperglycemic agent, acting to increase insulin sensitivity. There is a close relationship between obesity, insulin action, and development of type 2 diabetes. Withont listing additional peptides secreted by adipose tissue, it is important to understand that fat is an important player in human physiology. 

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