Fenofibrate improves βcell function by regulating pancreatic activities of ATPase and Ca2+release in high-fat diet induced Aged-C57 obese mice
10.13699/j.cnki.1001-6821.2015.10.031
- VernacularTitle:非诺贝特改善老年高脂喂养 C57小鼠胰岛β细胞功能及其作用机制研究
- Author:
Quan LIU
1
;
Shuai-Nan LIU
;
Shao-Cong HOU
;
Chun-Ming JIA
;
Yue WANG
;
Zhu-Fang SHEN
Author Information
1. 中国医学科学院 北京协和医学院 药物研究所天然药物活性物质与功能国家重点实验室
- Keywords:
fenofibrate;
high-fat diet induced Aged-C57 obese mice;
βcell function;
calcium ion
- From:
The Chinese Journal of Clinical Pharmacology
2015;(10):869-873,885
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the effects of the fenofibrate on glu-cose and lipids metabolism and beta cell function in high -fat diet in-duced Aged-C57 obese mice.Methods Male high-fat diet induced Aged-C57 obese mice selected by insulin tolerance test ( ITT) were di-vided into two groups , model group was orally administered by gavage with water , fenofibrate group at a dose of 100 mg? kg -1? d-1 for about 8 weeks.The C57 healthy mice was as normal group ( n =14 ) .Fasting plasma lipids , glucose , insulin levels were detected at the end of treat-ment.ITT and hyperglycemic clamp were determined .Pancreas morpho-logy changes and βcell mass were evaluated by hematoxylin -eosin and Gomori stainnings.The changes of mRNA expression in the pancreas were also analyzed by Real -time PCR.Results Fenofibrate signifi-cantly improved insulin sensitivity in high -fat diet induced Aged -C57 obese mice.Fasting plasma glucose , triglyceride and insulin levels were decreased increased after 50 days fenofibrate treatment ( P <0.01 , P<0.05, P<0.05).In addition, pancreatic Ca2+levels (P<0.05) and activities of ATPase (P<0.01) were also significantly increased after fenofibrate treatment .It was shown that fenofibrate up -regulated the pancreatic mRNA ex-pression of PDX1, INS1 and PKB (P<0.01, P<0.05, P<0.01).Moreover, the mRNA expression of RYR3 and SERCA2 associated with calcium ions release were increased in fenofibrate group (P<0.001, P<0.01).Conclusion These results indicated that chronic administration of fenofibrate improved dyslipidemia and glucose homeostasis in high-fat diet induced Aged-C57 obese mice , which is related to up-regulation of the pancreatic expression of some factors, which involved in insulin biosynthesis and calcium release .
