Insulins biological actions

Antidiabetic Drugs other than Insulin. Table 2 Tissue expression, ligands, genes activated, and biological actions of the peroxisome proliterator-activated receptor-y (PPARy)... 

Jones J, Clemmons D. 1995. Insulin-like growth factors and their binding proteins biological actions. Endo Rev 16 3-34. 

Commercial insulin preparations differ in a number of ways, such as differences in the recombinant DNA production techniques, amino acid sequence, concentration, solubility, and the time of onset and duration of their biologic action. 

Insulin binds to specific, high-affinity receptors in the cell membrane of most tissues, including liver, muscle, and adipose. This is the first step in a cascade of reactions ultimately leading to a diverse array of biologic actions. 

Phosphorylated IRS promotes activation of other protein kinases and phosphatases, reading to biologic actions of insulin. 

Bevan, A.P., P.G. Drake, J.F. Yale, A. Shaver, and B.I. Posner. 1995. Peroxovanadium compounds Biological actions and mechanism of insulin-mimesis. Mol. Cell. Bio-chem. 153 49-58. 

Polyclonal antibodies have been prepared against partially purified rabbit mammary gland receptors [42-44], and have been used to demonstrate that the receptors really are involved in mediating the biological actions of prolactin. Anti-receptor antibodies that blocked binding of labelled prolactin were able to inhibit prolactin-stimulated casein synthesis and amino acid transport in rabbit mammary gland explants in vitro [43,45] (Fig. 4). They had no effect on the actions of insulin... 

Vanadate (VOj or H2VO4 ) was first recognized in 1979 as having insulin mimetic properties [258]. Since then, vanadate and vanadyl (V ) have been shown to mimic most but not all biological actions of insulin in vitro and to lower blood glucose in streptozotocin-treated rats [259, 260]. Vanadate is a potent inhibitor of phosphotyrosine phosphatases, an interesting activity since the insulin receptor is a tyrosine kinase, and some of the actions of insulin have been proposed to take place via autophosphorylation of the insulin receptor and phosphorylation of cellular substrates on tyrosine residues [261]. Some recent developments on the mechanism and the in vivo activity of vanadate and its derivatives are presented here. 

At the cellular and molecular level, the binding of insulin to a specific membrane spanning receptor initiates a signal transduction cascade which ultimately produces the biological actions of the hormone. The insulin receptor is a tetrameric protein comprised of two a subunits that bind to insulin and two j3 subunits that are linked by disulfide bonds (55,56), and belongs to a subfamily of receptor typrosine kinases which also includes the insulin-like growth factor I (IGF-I) receptor. The a subunits are extracellularly located, while (S subunits span the membrane and have... 

Fig. 6.3 Insulin signaling pathways. Possible routes through which insulin can promote its diverse biological actions Cell proliferation, gluconeogenesis, lipolysis and glycogen syn-...

The importance of the biological actions of insulin on target cells is underscored by defects in any of the five steps involved in receptor function. These steps are analogous to the scheme described for LDL receptor gene defects (Chapter 20). Mutations can lead to ... 

Zapf,., Schoenle, E., and Froesch, E. R., Insulin-like growth fuitors 1 and 11 Some biological actions and receptor binding characteristics of two purified constituents of nonsuppressible insulin-like activity of human serum. Ear. J. Biochem. 87, 285-296... 

The insulin receptor in rat liver membranes has been found to interact with another membrane glycoprotein that may represent either a non-recognition portion of the receptor oligomer, or an effector molecule related to the biological action of insulin. ... 

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