Growth Insulin effect

Growth promoting effects of insulin occur via interaction of the IR with Grb-2 or SHC adaptor proteins. The cascade from Grb-2 or SHC includes ras, raf, sos and MEK, culminating in activation of the gene transcription factor MAPK. Refer again to Figure 4.21. 

Crans, D.C., L. Yang, J.A. Alfano, L.-H. Chi, W. Jin, M. Mahroof-Tahir, K. Robbins, M.M. Toloue, L.K. Chan, A.J. Plante, R.Z. Grayson, and G.R. Willsky. 2003. (4-Hydroxypyridine-2,6-dicarboxylato)oxovanadate(V)—a new insulin-like compound Chemistry, effects on myoblast and yeast cell growth and effects on hyperglycemia in rats with STZ-induced diabetes. Coord. Chem. Rev. 237 13-22. 

Sun YN, Lee JH, Almon RR, Jusko WJ. A pharmacokinetic/pharmacod5mamic model for recombinant human growth hormone. Effects on induction of insulin-like growth factor 1 in monkeys. J Pharmacol Exp Ther 1999 89 1523-32. 

Gr0nbaek H, Frystyk J, 0rskov H, et al. 1995. Effect of sodium selenite on growth, insulin-like growth factor-binding proteins and insulin-like growth factor-I in rats. J Endocrinol 145 105-112. 

Since the original description of Detrisac et al. [46] a 1 1 mixture of DMEM and HAMF12, supplemented with hydrocortisone, triiodothyronine, insulin, transferrin and selenate (currently known as K1 medium) [51], has been the most widely used medium in human (proximal) tubular epithelial cell culture. Several authors add serum because of its growth promoting effect. 

GH is only one of many honnones involved in growth. Others are thyroxine, cortisol, the sex steroids, insulin, and a number of paracrine growth factors, particularly the somatomedins or insulin-like growth factors (IGFs) which mediate the growth promoting effects ol growth hormone. 

Mill, J.F., Chao, M.V. and Ishii, D.N. (1985) Insulin, insulinlike growth factor II and nerve growth factor effects on tubulin mRNA levels and neurite formation. Proc. Natl. Acad. Sci. USA 82 7126-7130. 

Recio-Pinto, E. and Ishii, D.N. (1988b) Insulin and related growth factors- effects on the nervous system and mechanism for neurite growth and regeneration. Neurochem. Int. 12 397-414. 

Sun Y N, Lee H J, Almon R R, et al. (1999). A pharmacokinetic/pharmacodynamic model for recombinant hnman growth hormone effects on induction of insulin-like growth factor I in monkeys. J. Pharmacol. Exp. Ther. 289 1523-1532. 

This insulin effect of growth hormone observed in vivo may also explain some of the discrepancies observed between in vivo and in vitro effects of growth hormones on glucose uptake by muscle. Whereas growth hormone inhibits glucose uptake in vitro, in vivo its inhibitory effect is compensated for by the insulin secreted as a result of liver gluconeogenesis. 

The administration of growth hormone to hypophysectomized animals relieves the insulin hypersensitivity and may even create some insulin resistance. In addition to its insulinic effect, growth hormone seems to have another effect on muscle that manifests itself several hours after the administration of the hormone—decreased glucose uptake and decreased insulin sensitivity. The time lapse between the injection and the manifestation suggests that the effect may result from metabolic by-products of growth hormone. 

Skeletal growth in acromegaly cannot simply be explained by an anti-insulinic effect, stimulation of lipolysis, or stimulation of protein synthesis because cartilage formation requires that collagen (conversion of protein to hydroxyproline) and cartilage (synthesis of chondroitin sulfate) be formed. Acromegalic serum... 

The role of insulin receptors in stimulation of growth is puzzling. Substances like lectins and concanavalin A, which are capable of eliciting an insulin effect, also stimulate mitosis. Insulin stimulates mitosis in some tissue, for example, the mammary gland. Whether the lectins bind to insulin receptors to stimulate mitosis is not known. The fact is that lectins are capable of stimulating mitosis in cells devoid of insulin receptors such as lymphocytes, possibly because the lymphocyte contains partial insulin receptors. But it cannot be excluded that lectins act at other sites of the membrane at one or more steps in the chain that leads from insulin binding to mitosis. The interpretation of the... 

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