Adenovirus vector-mediated macrophage erythroblast attacher (MAEA) overexpression in primary mouse hepatocytes attenuates hepatic gluconeogenesis

Biochemistry and Biophysics Reports

Fuminori Sakurai¹  Hiroyuki Mizuguchi¹  Minako Okamoto²  Toru Nishinaka²  Kahori Shimizu²  Tomoyuki Terada²  Koji Tomita³ 

[1] Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan;Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Osaka 584-8540, Japan;Laboratory of Molecular Biology, Faculty of Pharmacy, Osaka Ohtani University, Osaka 584-8540, Japan;

关键词: Adenovirus vector;    Diabetes mellitus;    Glucose metabolism;    GWAS;    MAEA;   

DOI  :  10.1016/j.bbrep.2017.04.010

来源: DOAJ

【 摘 要 】

Japanese patients with type 2 diabetes mellitus present a different responsiveness in terms of insulin secretion to glucose and body mass index (BMI) from other populations. The genetic background that predisposes Japanese individuals to type 2 diabetes mellitus is under study. Recent genetic studies demonstrated that the locus mapped in macrophage erythroblast attacher (MAEA) increases the susceptibility to type 2 diabetes mellitus in East Asians, including Japanese individuals. MAEA encodes a protein that plays a role in erythroblast enucleation and in the normal differentiation of erythroid cells and macrophages. However, the contribution of MAEA to type 2 diabetes mellitus remains unknown. In this study, to overexpress MAEA in the mouse liver and primary mouse hepatocytes, we generated a MAEA-expressing adenovirus (Ad) vector using a novel Ad vector exhibiting significantly lower hepatotoxicity (Ad-MAEA). Blood glucose and insulin levels in Ad-MAEA-treated mice were comparable to those in control Ad-treated mice. Primary mouse hepatocytes transduced with Ad-MAEA showed lower levels of expression of gluconeogenesis genes than those transduced with the control Ad vector. Hepatocyte nuclear factor-4α (HNF-4α) mRNA expression in primary mouse hepatocytes was also suppressed by MAEA overexpression. These results suggest that MAEA overexpression attenuates hepatic gluconeogenesis, which could potentially lead to improvement of type 2 diabetes mellitus.

【 授权许可】

Unknown