Insulin endocytosis

Receptor-mediated endocytosis may be possible because receptors have a high affinity for BDNF (Deckner et al. 1993). A linear relation between intranasal administration of -labeled NGF and brain concentrations of the compound suggest that this transportation is not mediated by receptors and that this releasing method of agents to the brain via olfactory nerves may be effective for many therapies (Frey et al. 1995). BDNF and the insulin-type growth factor (IGF-1) are currently used in clinical studies (Appel 1997). 

Figure 5.6. Metabolism of proteins by proteases found at the cell surface and internal cellular organelles. Intracellular uptake of proteins often involved receptor-mediated endocytosis initial surface binding can be specific for a hormone (e.g., insulin, glucagon).

Huckett, B., Ariatti, M., Hawtrey, A.O. (1990). Evidence for targeted gene transfer by receptor-mediated endocytosis. Stable expression following insulin-directed entry of NEO into HepG2 cells. Biochem. Pharm., 40, 253-263. 

When insulin level drops, glucose transporters are removed from the plasma membrane by endocytosis, forming small vesicles. 

Fan, J.Y., et al. 1982. Receptor-mediated endocytosis of insulin Role of microvilli, coated pits, and coated vesicles. Proc Natl Acad Sci 79 7788. 

Gupta, A.K., et al. 2003. Receptor-mediated targeting of magnetic nanoparticles using insulin as a surface ligand to prevent endocytosis. IEEE Trans Nanobioscience 2 255. 

R. L. Roberts and A. Sandra, Receptor-mediated endocytosis of insulin by cultured endothelial cells. Tissue Cell 24 603-611 (1992). 

Matsumoto, K. et al., Insulin enhances macrophage scavenger receptor-mediated endocytotic uptake of advanced glycation endproducts, J. Biol. Chem. 273,8630-8637,1998). There is some interest in receptor-mediated endocytosis for drug delivery (Selbo, P.K., Hogset, A., Prasmickaite, L., and Berg, K Photochemical internalization a novel dmg delivery system. Tumour Biol. 23, 102-112, 2002). 

Endocytosis is a normal mechanism for protein and insulin reabsorption at the proximal tubule of the kidney. A considerable amount of insulin (50%) is metabolized by the kidney, which may account, at least in part, for the decreased insuhn requirement that occurs in diabetic patients with decreased renal function. Furthermore, this uptake process allows highly hydrophilic hpid insoluble drugs such as aminoglyco-... 

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