Insulin receptor signal transduction

Loss of the cell s responsiveness to the hormone insulin caused by pathological alterations in the insulin receptor signal transduction pathway, and often leading... 

S. J. Hunter and T. Garvey Insulin action and insulin resistance Diseases involving defects in insulin receptors, signal transduction, glucose transport effector system. American Journal of Medicine 105, 331 (1998). 

As work with vanadium compounds and diabetes in cell system has continued, it has become clear that there are also insulin-independent mechanisms at work. One insulin-independent signal transduction pathway appears to be involved in glycogen metabolism reactions in rat adipocytes [137] that also involve PI-3K. A major difference was that only vanadate promoted glycogenesis through the activation of a cytosolic protein tyrosine kinase, which was mediated in an insulin receptor-independent manner. 

On the other hand, berberine is also able to induce the expressirui of insulin receptors (at least in liver) in a dose-dependent manner, through upregulation of insulin receptor mRNA [28, 29]. This effect was dependent on the presence of insulin. Berberine has also been linked to improving post-receptor signal transduction [24]. 

Like other growth factors, the IDGFs presumably activate a signal transduction pathway that ultimately controls transcription and replication. One possibility is that they interact in some way with the insulin receptor (InsR) pathway, which has... 

Ruan Y, Chen C, Cao Y, Garofalo RS 1995 The Drosophila insulin receptor contains a novel carboxyl-terminal extension likely to play an important role in signal transduction. J Biol Chem 270 4236-4243... 

Dupont J, Le Roith D. 2001. Insulin and insulin-Uke growth factor I receptors similarities and differences in signal transduction, Horm Res 55(suppl 2) 22-26. 

In contrast to the receptors for insulin and growth factors (see p. 388), the cytokine receptors (with a few exceptions) have no tyrosine kinase activity. After binding of cytokine (1), they associate with one another to form homodimers, join together with other signal transduction proteins (STPs) to form dimers, or promote dimerization of other... 

The insulin receptor substrate IRS couples the insulin receptor to sequential effector molecules (review Ogawa et al., 1998). On binding of insulin to the insulin receptor, the tyrosine kinase activity of the receptor is stimulated. The IRS protein is phosphory-lated at several Tyr residues, which then serve as attachment points for sequential effector molecules as e.g. the Grb2-mSos complex, the P13-kinase and the protein tyrosine phosphatase SHP-2. The IRS protein also has a phosphotyrosine binding domain and a PH domain. Both modules are required for signal transduction in vivo. It is assumed that the PTB domain binds to autophosphorylation sites of the insulin receptor and that the PH domain is involved in membrane association of IRS. 

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