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Lack of GPR40/FFAR1 does not induce diabetes even under insulin resistance condition.
Matsuda-Nagasumi, K; Takami-Esaki, R; Iwachidow, K; Yasuhara, Y; Tanaka, H; Ogi, K; Nakata, M; Yano, T; Hinuma, S; Taketomi, S; Odaka, H; Kaisho, Y.
Afiliação
  • Matsuda-Nagasumi K; Metabolic Disease Drug Discovery Unit, Takeda Pharmaceutical Company Limited, Kanagawa, Japan. kae.matsuda@takeda.com
Diabetes Obes Metab ; 15(6): 538-45, 2013 Jun.
Article em En | MEDLINE | ID: mdl-23331570
ABSTRACT

AIMS:

G protein-coupled receptor/free fatty acid receptor 1 (GPR40/FFAR1 ) regulates free fatty acid-induced insulin secretion. This study has been performed to clarify whether or not loss of GPR40/FFAR1 function exacerbates diabetes, that is, whether GPR40 has an essential physiological role in the development of diabetes or not.

METHODS:

We generated GPR40/FFAR1 knockout (KO) mice and analysed their phenotypes in vitro and in vivo under the condition of dietary or genetically induced insulin resistance.

RESULTS:

GPR40/FFAR1 KO mice kept on a high-fat diet became obese, developed glucose intolerance to a similar degree as GPR40/FFAR1 wild-type (WT) mice. In addition, the phenotype of KO mice harbouring diabetogenic KK background genes showed glucose intolerance at a level similar to level for control KK mice. In both mouse models with insulin resistance, insulin secretion after oral glucose load and homeostasis model assessment-insulin resistance (HOMA-IR) did not change between GPR40/FFAR1 KO and WT mice. Although glucose-induced insulin secretion under high palmitate concentration was significantly lower in KO than in WT islets, pancreatic insulin content and insulin secretion stimulated with glucose alone were not different between KO and WT mice.

CONCLUSIONS:

GPR40/FFAR1 has a major role in regulating fatty-acid-mediated insulin secretion, but the lack of GPR40/FFAR1 does not exacerbate glucose intolerance and insulin resistance induced by high-fat diet or diabetogenic KK gene. Our findings indicate that loss of GPR40/FFAR1 function does not play an important role in inducing or exacerbating diabetes.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pâncreas / Receptores Acoplados a Proteínas G / Diabetes Mellitus Experimental / Insulina Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pâncreas / Receptores Acoplados a Proteínas G / Diabetes Mellitus Experimental / Insulina Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2013 Tipo de documento: Article