Small Molecule Activators of the Insulin Receptor: Potential New Therapeutic Agents for the Treatment of Diabetes Mellitus

Laborde, Edgardo; Manchem, Vara Prasad
December 2002
Current Medicinal Chemistry;Dec2002, Vol. 9 Issue 24, p2231
Academic Journal
Diabetes mellitus refers to a spectrum of syndromes characterized by abnormally high levels of glucose in blood. These syndromes are associated with an absolute (Type 1 diabetes) or relative (Type 2 diabetes) deficiency of insulin, coupled with varying degrees of peripheral resistance to the actions of insulin. Clinical studies have shown that controlling hyperglycemia significantly reduces the appearance and progression of the vascular complications associated with diabetes. Insulin's regulation of glucose homeostasis is mediated by a cascade of signaling events that take place upon insulin binding to its cell surface receptor. Autophosphorylation of the receptor and activation of its intrinsic tyrosine kinase are critical processes for transmitting these intracellular signals. Type 1 diabetes patients depend on exogenous insulin to achieve these effects, whereas Type 2 diabetes patients can accomplish a similar response through oral medications that increase the production of endogenous insulin or enhance its actions on the target tissues. Current biochemical and clinical evidence suggests that defects within the insulin receptor itself may be a cause of insulin resistance leading to Type 2 diabetes. This review focuses on the insulin receptor as a target for therapeutic intervention, and describes the recent discovery of small molecules that act on the receptor and either enhance or directly emulate the actions of insulin both in vitro and in vivo.


Related Articles

  • Developmental biology: Gender benders. Koopman, Peter // Nature;11/20/2003, Vol. 426 Issue 6964, p241 

    A painstaking triple-gene-knockout study has revealed a crucial role for insulin receptors in male sexual development.

  • When a domain is not a domain. Park, Sang Youn; Shoelson, Steven E. // Nature Structural & Molecular Biology;Mar2008, Vol. 15 Issue 3, p224 

    The article provides information on the kinase regulatory-loop binding (KRLB). KRLB was once considered as a domain that has adhering properties analogous to phosphotyrosine binding (PTB) domains. However, a study showed that KLRB is a short peptide segment that conjugates to insulin receptor to...

  • © THE ERYTHROCYTE INSULIN RECEPTOR. McElduff, A.; Eastman, C. J. // Australian Journal of Experimental Biology & Medical Science;Aug1981, Vol. 59 Issue 4, p439 

    Discusses the development of a precise, reproducible radioreceptor assay for insulin receptors in human erythrocytes. Mean specific binding in 11 normal volunteers; Results of calculating the intra- and inter assay coefficients of variation; Inverse relationship between specific binding and...

  • Novel Covalently Linked Insulin Dimer Engineered to Investigate the Function of Insulin Dimerization. Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.; Huus, Kasper; Schlein, Morten; Pedersen, Thomas �.; Kjeldsen, Thomas; Jensen, Knud J.; Hub�lek, Franti�ek // PLoS ONE;Feb2012, Vol. 7 Issue 2, p1 

    An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...

  • Oral Insulin-Mimetic Compounds That Act Independently of Insulin. García-Vicente, Silvia; Yraola, Francesc; Marti, Luc; González-Muñoz, Elena; García-Barrado, María José; Cantó, Carles; Abella, Anna; Bour, Sandy; Artuch, Rafael; Sierra, Cristina; Brandi, Nuria; Carpéné, Christian; Moratinos, Julio; Camps, Marta; Palacín, Manuel; Testar, Xavier; Gumà, Anna; Albericio, Fernando; Royo, Miriam; Mian, Alec // Diabetes;Feb2007, Vol. 56 Issue 2, p486 

    The hallmarks of insulin action are the stimulation and suppression of anabolic and catabolic responses, respectively. These responses are orchestrated by the insulin pathway and are initiated by the binding of insulin to the insulin receptor, which leads to activation of the receptor's...

  • FUNCTIONAL GENOMICS: Insulin ? meet the family. Patterson, Mark // Nature Reviews Genetics;Apr2001, Vol. 2 Issue 4, p243 

    Discusses research being done on the regulation of insulin receptor DAF-2 signaling by human insulin and ins-1, one of the Caenorhabditis elegans genes. Reference to a study by Pierce et al; Candidates for endogenous insulin signals in Caenorhabditis elegans.

  • Overexpression of Suppressor of Cytokine Signaling 3 in Adipose Tissue Causes Local but Not Systemic Insulin Resistance. Shi, Hang; Cave, Belinda; Inouye, Karen; Bjørbæk, Christian; Flier, Jeffrey S. // Diabetes;Mar2006, Vol. 55 Issue 3, p699 

    In adipocytes, suppressor of cytokine signaling (SOCS)3 deficiency increases insulin-stimulated insulin receptor substrate (IRS)-1 and -2 phosphorylation, IRS-associated phosphatidylinositol 3 kinase activity, and insulin-stimulated glucose uptake. Moreover, SOCS3 is required for tumor necrosis...

  • GYM GEM. Stoppani, Jim // Joe Weider's Muscle & Fitness;Dec2006, Vol. 67 Issue 12, p216 

    This article discusses the nutritional benefits of the herb Gymnema sylvestre. The herb helps increase insulin sensitivity, and increases insulin secretion to the pancreas. More insulin can lead to a greater anabolic response, and can increase muscle growth after workouts. The author advises...

  • Lack of Arg972 Polymorphism in the IRS1 Gene in Parakanã Brazilian Indians. Bezerra, Rosângela M. N.; Chadid, Thiago T.; Altemani, Claúdia M.; Sales, Teresa S. I.; Menezes, Raimundo; Soares, Manoel C. P.; Saad, Sara T. O.; Saad, Mario J. A. // Human Biology;Feb2004, Vol. 76 Issue 1, p147 

    Several polymorphisms in the insulin receptor substrate-1 (IRS1) gene have been reported in the last years. The most common IRS1 variant, a Gly →Arg substitution at codon 972 (Arg972 IRS1), is more prevalent among subjects who have features of insulin resistance syndrome associated, or...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics