Exp Clin Endocrinol Diabetes 2022; 130(04): 254-261
DOI: 10.1055/a-1400-2656
Article

ZFAND3 Overexpression in the Mouse Liver Improves Glucose Tolerance and Hepatic Insulin Resistance

Kahori Shimizu
1   Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
,
Yuya Ogiya
1   Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
,
Kaede Yoshinaga
1   Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
,
Hajime Kimura
1   Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
,
Shotaro Michinaga
2   Laboratory of Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
,
Moe Ono
3   Laboratory of Molecular Biology, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
,
Ayako Taketomi
1   Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
,
Tomoyuki Terada
1   Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
,
Fuminori Sakurai
4   Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
,
Hiroyuki Mizuguchi
4   Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
5   The Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka, Japan
6   Laboratory of Hepatocyte Differentiation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan
7   Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.
,
Koji Tomita
3   Laboratory of Molecular Biology, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
,
Toru Nishinaka
1   Laboratory of Biochemistry, Faculty of Pharmacy, Osaka Ohtani University, Osaka, Japan
› Author Affiliations
Funding: This study was supported by JSPS KAKENHI (grant numbers: JP15K18939 and JP18K14964) and the Osaka Ohtani University Research Foundation (KS).

Abstract

Genome-wide association studies have identified more than 300 loci associated with type 2 diabetes mellitus; however, the mechanisms underlying their role in type 2 diabetes mellitus susceptibility remain largely unknown. Zinc finger AN1-type domain 3 (ZFAND3), known as testis-expressed sequence 27, is a type 2 diabetes mellitus-susceptibility gene. Limited information is available regarding the physiological role of ZFAND3 in vivo. This study aimed to investigate the association between ZFAND3 and type 2 diabetes mellitus. ZFAND3 was significantly upregulated in the liver of diabetic mice compared to wild-type mice. To overexpress ZFAND3, we generated a ZFAND3-expressing adenovirus (Ad) vector using an improved Ad vector exhibiting significantly lower hepatotoxicity (Ad-ZFAND3). Glucose tolerance was significantly improved in Ad-ZFAND3-treated mice compared to the control Ad-treated mice. ZFAND3 overexpression in the mouse liver also improved insulin resistance. Furthermore, gluconeogenic gene expression was significantly lower in primary mouse hepatocytes transduced with Ad-ZFAND3 than those transduced with the control Ad vector. The present results suggest that ZFAND3 improves glucose tolerance by improving insulin resistance and suppressing gluconeogenesis, serving as a potential novel therapeutic target for type 2 diabetes mellitus.

Supplementary Material



Publication History

Received: 11 September 2020
Received: 02 February 2021

Accepted: 25 February 2021

Article published online:
29 March 2021

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