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Oral insulin-mimetic compounds that act independently of insulin.
Diabetes 2007; 56(2):486-93D

Abstract

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 intrinsic tyrosine kinase. Severe defects in the insulin pathway, such as in types A and B and advanced type 1 and 2 diabetes lead to severe insulin resistance, resulting in a partial or complete absence of response to exogenous insulin and other known classes of antidiabetes therapies. We have characterized a novel class of arylalkylamine vanadium salts that exert potent insulin-mimetic effects downstream of the insulin receptor in adipocytes. These compounds trigger insulin signaling, which is characterized by rapid activation of insulin receptor substrate-1, Akt, and glycogen synthase kinase-3 independent of insulin receptor phosphorylation. Administration of these compounds to animal models of diabetes lowered glycemia and normalized the plasma lipid profile. Arylalkylamine vanadium compounds also showed antidiabetic effects in severely diabetic rats with undetectable circulating insulin. These results demonstrate the feasibility of insulin-like regulation in the complete absence of insulin and downstream of the insulin receptor. This represents a novel therapeutic approach for diabetic patients with severe insulin resistance.

Authors+Show Affiliations

Institute for Research in Biomedicine, Josep Samitier 1-5, Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17259395

Citation

García-Vicente, Silvia, et al. "Oral Insulin-mimetic Compounds That Act Independently of Insulin." Diabetes, vol. 56, no. 2, 2007, pp. 486-93.
García-Vicente S, Yraola F, Marti L, et al. Oral insulin-mimetic compounds that act independently of insulin. Diabetes. 2007;56(2):486-93.
García-Vicente, S., Yraola, F., Marti, L., González-Muñoz, E., García-Barrado, M. J., Cantó, C., ... Zorzano, A. (2007). Oral insulin-mimetic compounds that act independently of insulin. Diabetes, 56(2), pp. 486-93.
García-Vicente S, et al. Oral Insulin-mimetic Compounds That Act Independently of Insulin. Diabetes. 2007;56(2):486-93. PubMed PMID: 17259395.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral insulin-mimetic compounds that act independently of insulin. AU - García-Vicente,Silvia, AU - Yraola,Francesc, AU - Marti,Luc, AU - González-Muñoz,Elena, AU - García-Barrado,María José, AU - Cantó,Carles, AU - Abella,Anna, AU - Bour,Sandy, AU - Artuch,Rafael, AU - Sierra,Cristina, AU - Brandi,Nuria, AU - Carpéné,Christian, AU - Moratinos,Julio, AU - Camps,Marta, AU - Palacín,Manuel, AU - Testar,Xavier, AU - Gumà,Anna, AU - Albericio,Fernando, AU - Royo,Miriam, AU - Mian,Alec, AU - Zorzano,Antonio, PY - 2007/1/30/pubmed PY - 2007/4/10/medline PY - 2007/1/30/entrez SP - 486 EP - 93 JF - Diabetes JO - Diabetes VL - 56 IS - 2 N2 - 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 intrinsic tyrosine kinase. Severe defects in the insulin pathway, such as in types A and B and advanced type 1 and 2 diabetes lead to severe insulin resistance, resulting in a partial or complete absence of response to exogenous insulin and other known classes of antidiabetes therapies. We have characterized a novel class of arylalkylamine vanadium salts that exert potent insulin-mimetic effects downstream of the insulin receptor in adipocytes. These compounds trigger insulin signaling, which is characterized by rapid activation of insulin receptor substrate-1, Akt, and glycogen synthase kinase-3 independent of insulin receptor phosphorylation. Administration of these compounds to animal models of diabetes lowered glycemia and normalized the plasma lipid profile. Arylalkylamine vanadium compounds also showed antidiabetic effects in severely diabetic rats with undetectable circulating insulin. These results demonstrate the feasibility of insulin-like regulation in the complete absence of insulin and downstream of the insulin receptor. This represents a novel therapeutic approach for diabetic patients with severe insulin resistance. SN - 0012-1797 UR - https://www.unboundmedicine.com/medline/citation/17259395/Oral_insulin_mimetic_compounds_that_act_independently_of_insulin_ L2 - http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=17259395 DB - PRIME DP - Unbound Medicine ER -