Adenovirus vector-mediated macrophage erythroblast attacher (MAEA) overexpression in primary mouse hepatocytes attenuates hepatic gluconeogenesis |
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| Authors: | Kahori Shimizu Minako Okamoto Tomoyuki Terada Fuminori Sakurai Hiroyuki Mizuguchi Koji Tomita Toru Nishinaka |
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| Affiliation: | 1. Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Osaka 584-8540, Japan;2. Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan;3. Laboratory of Regulatory Sciences for Oligonucleotide Therapeutics, Clinical Drug Development Unit, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan;4. Global Center for Medical Engineering and Informatics, Osaka University, Osaka 565-0871, Japan;5. Laboratory of Hepatocyte Differentiation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan;6. iPS Cell-Based Research Project on Hepatic Toxicity and Metabolism, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan;7. Laboratory of Molecular Biology, Faculty of Pharmacy, Osaka Ohtani University, Osaka 584-8540, Japan |
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| Abstract: | 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. |
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| Keywords: | Adenovirus vector Diabetes mellitus Glucose metabolism GWAS MAEA |
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