Insulin and growth factors

Prenylation of proteins (a posttranslational modification) that need to be held in the cell membrane by a lipid tail. An example is the p21 G protein in the insulin and growth factor pathways. 

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... 

P. Cohen. Dissection of the protein phosphorylation cascades involved in insulin and growth factor action. Biochem Soc Trans, 21, 555-567, 1993. 

Insulin and Amylin. Insulin is a member of a family of related peptides, the insulin-like growth factors (IGFs), including IGF-I and IGF-II (60) and amylin (75), a 37-amino acid peptide that mimics the secretory pattern of insulin. Amylin is deficient ia type 1 diabetes meUitus but is elevated ia hyperinsulinemic states such as insulin resistance, mild glucose iatolerance, and hypertension (33). Insulin is synthesized ia pancreatic P cells from proinsulin, giving rise to the two peptide chains, 4. and B, of the insulin molecule. IGF-I and IGF-II have stmctures that are homologous to that of proinsulin (see INSULIN AND OTHER ANTIDIABETIC DRUGS). 

Bouaboula, M., Perrachon, S., Milligan, L., Canatt, X., Rinaldi-Carmona, M., Portier, M., Barth, F., Calandra, B., Pecceu, F., Lupker, J., Maffrand, J.-P., Le Fur, G., and Casellas, P. (1997). A selective inverse agonist for central cannabinoid receptor inhibits mitogen-activated protein kinase activation stimulated by insulin or insulin-like growth factor. J. Biol. Ckem. 272 22330-22339. 

In addition to insulin, the INSR can also bind insulin-like growth factors (IGF1 and IGF2) albeit with considerably lower affinity (2 and 3 orders of magnitude, respectively). 

Family of enzymes phosphorylating phosphatidylinositol (Ptdlns), PtdIns(4)phosphate, and PtdIns(4,5)phosphate in the 3-position. The Ptdlns(3 phospholipids are second messengers in processes like cell growth, cytoskeletal rearrangement, and vesicular transport. PI 3-kinases are heterodimers composed of a catalytic and a regulatory subunit. The enzymes are activated by insulin, many growth factors, and by a variety of cytokines. Their activity can be inhibited by wortmannin and LY294002. 

Figure 38-7. Activation of elF-4E by insulin and formation of the cap binding elF-4F complex. The 4F-cap mRNA complex is depicted as in Figure 38-6. The 4F complex consists of elF-4E (4E), elF-4A, and elF-4G. 4E is inactive when bound by one ofa family of binding proteins (4E-BPs). Insulin and mitogenic factors (eg, IGF-1, PDGF, interleukin-2, and angiotensin II) activate a serine protein kinase in the mTOR pathway, and this results in the phosphorylation of 4E-BP. Phosphorylated 4E-BP dissociates from 4E, and the latter is then able to form the 4F complex and bind to the mRNA cap. These growth peptides also phosphorylate 4E itself by activating a component of the MAP kinase pathway. Phosphorylated 4E binds much more avidly to the cap than does nonphosphorylated 4E.

Insulin-like growth factors I and II Nerve growth factor Platelet-derived growth factor Prolactin... 

ARJMANDI B H, KHALIL D A and HOLLIS B w (2002), Soy protein its effects on intestinal calcium transport, serum vitamin D and insulin-like growth factor-1 in ovariectomized rats. Calcif Tissue Int 70(6), 483-7. 

KHALIL D A, LUCAS E A, lUMA S, SMITH B J, PAYTON M E and ARJMANDI B H (2002) Soy prOteiu supplementation increases serum insulin-like growth factor-1 in young and old men but does not affect markers of bone metabolism. J Nutr 132, 2605-8. 

Karas, M. et ah. Lycopene interferes with cell cycle progression and insulin-like growth factor I signaling in mammary cancer cells, Nutr. Cancer, 36,101, 2000. 

Fahrner, R.L., Lester, P.M., Blank, G.S., and Reifsnyder, D. H., Non-flammable preparative reversed-phase liquid chromatography of recombinant human insulin-like growth factor-I, ]. Chromatogr. A, 830, 127, 1999. 

Dopamine agonists may be appropriate for patients with mildly elevated insulin-like growth factor I levels who have growth hormone and prolactin co-secreting tumors. 

Prolonged exposure to elevated growth hormone and insulin-like growth factor I levels can lead to serious complications in patients with acromegaly. Aggressively manage... 

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