RESUMO
G-protein coupled receptor 119 (GPR119) has emerged as a promising new target for the treatment of type 2 diabetes mellitus. The expression of GPR119 on the pancreatic B cells and intestinal L cells provides a unique opportunity for a single drug to promote insulin and GLP-1 secretion. In this study, we identified a novel small molecule GPR119 agonist, HD0471953, from our large library of synthetic compounds based on its ability to anti-hyperglycemic effects on T2DM murine models. We have tested the acute efficacy of HD0471953 by the oral glucose tolerance test (OGTT) with normal C57BL/6J mice. Then, chronic administrations of HD0471953 were performed to evaluate the efficacy on various diabetic rodent models. Single administration of HD0471953 showed improved glycemic control with a dose-dependent manner in OGTT with normal mice, and the insulin and GLP-1 were also increased. To identify chronic efficacy, we have observed a decline of blood glucose and fasting insulin in a dose-dependent manner of 10, 20, and 50 mpk in db/db mice. The results suggest that HD0471953 may be a potentially promising anti-hyperglycemic agent for the treatment of patients with type 2 diabetes mellitus.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Receptores Acoplados a Proteínas G/agonistas , Animais , Glicemia/metabolismo , Células Cultivadas , AMP Cíclico/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/patologia , Avaliação Pré-Clínica de Medicamentos , Teste de Tolerância a Glucose , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resultado do TratamentoRESUMO
In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at Assuntos
Anti-Infecciosos/farmacologia
, Anti-Infecciosos/uso terapêutico
, Infecções por Bactérias Gram-Positivas/tratamento farmacológico
, Cocos Gram-Positivos/efeitos dos fármacos
, Oxazolidinonas/farmacologia
, Oxazolidinonas/uso terapêutico
, Acetamidas/farmacologia
, Acetamidas/uso terapêutico
, Aerobiose
, Animais
, Farmacorresistência Bacteriana
, Infecções por Bactérias Gram-Positivas/microbiologia
, Cocos Gram-Positivos/crescimento & desenvolvimento
, Humanos
, Linezolida
, Masculino
, Camundongos
, Camundongos Endogâmicos ICR
, Testes de Sensibilidade Microbiana