GQ-16, a Novel Peroxisome Proliferator-activated Receptor γ (PPARγ) Ligand, Promotes Insulin Sensitization without Weight Gain

Amato, Angélica A.; Rajagopalan, Senapathy; Lin, Jean Z.; Carvalho, Bruno M.; Figueira, Ana C.  M.; Lu, Jenny; Ayers, Stephen D.; Mottin, Melina; Silveira, Rodrigo L.; Souza, Paulo C.  T.; Mourão, Rosa H.  V.; Saad, Mário J.  A.; Togashi, Marie; Simeoni, Luiz A.; Abdalla, Dulcinéia S.  P.; Skaf, Munir S.; Polikparpov, Igor; Lima, Maria C.  A.; Galdino, Suely L.; Brennan, Richard G.; Baxter, John D.; Pitta, Ivan R.; Webb, Paul; Phillips, Kevin J.; Neves, Francisco A.  R.

doi:10.1074/jbc.m111.332106

GQ-16, a Novel Peroxisome Proliferator-activated Receptor γ (PPARγ) Ligand, Promotes Insulin Sensitization without Weight Gain

Journal Article · Mon May 14 00:00:00 EDT 2012 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.m111.332106· OSTI ID:1625076

Amato, Angélica A. ^[1]; Rajagopalan, Senapathy ^[2]; Lin, Jean Z. ^[3]; Carvalho, Bruno M. ^[4]; Figueira, Ana C. M. ^[5]; Lu, Jenny ^[2]; Ayers, Stephen D. ^[2]; Mottin, Melina ^[6]; Silveira, Rodrigo L. ^[6]; Souza, Paulo C. T. ^[6]; Mourão, Rosa H. V. ^[7]; Saad, Mário J. A. ^[4]; Togashi, Marie ^[8]; Simeoni, Luiz A. ^[8]; Abdalla, Dulcinéia S. P. ^[9]; Skaf, Munir S. ^[6]; Polikparpov, Igor ^[10]; Lima, Maria C. A. ^[11]; Galdino, Suely L. ^[11]; Brennan, Richard G. ^[12] more »

Universidade de Brasília (Brazil). Faculdade de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Laboratório de Farmacologia Molecular; DOE/OSTI
Methodist Hospital Research Institute, Houston, TX (United States). Diabetes Research Center
Univ. of Houston, TX (United States). Center for Nuclear Receptors and Cell Signaling. Dept. of Biology and Biochemistry
Universidade Estadual de Campinas, São Paulo (Brazil). Departamento de Medicina Interna
Brazilian Association for Synchrotron Light Technology, São Paulo (Brazil). National Inst. of Biosciences
Univ. of Campinas (UNICAMP), Sao Paulo (Brazil). Inst. of Chemistry
Universidade Federal do Oeste do Pará (Brazil). Laboratório de Bioprospecça˜o e Biologia Experimental
Universidade de Brasília (Brazil). Faculdade de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Laboratório de Farmacologia Molecular
Univ. of Sao Paulo (Brazil). Faculdade de Ciências Farmacêuticas. Departamento de Analises Clínicas e Toxicológicas
Univ. of Sao Paulo (Brazil). Instituto de Física de São Carlos. Departamento de Física
Universidade Federal de Pernambuco (Brazil). Departamento de Antibióticos
Duke Univ., Durham, NC (United States). Medical Center. Dept. of Biochemistry

Background: PPARγ agonists improve insulin sensitivity but also evoke weight gain. Results: GQ-16 is a PPARγ partial agonist that blocks receptor phosphorylation by Cdk5 and improves insulin sensitivity in diabetic mice in the absence of weight gain. Conclusion: The unique binding mode of GQ-16 appears to be responsible for the compound’s advantageous pharmacological profile. Significance: Similar compounds could have promise as anti-diabetic therapeutics.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1625076

Journal Information:: Journal of Biological Chemistry, Journal Name: Journal of Biological Chemistry Journal Issue: 33 Vol. 287; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: English

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