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Original Research

Open Access

Knockdown of HNF1A improves type 2 diabetes combined with non-alcoholic fatty liver and glucose and lipid metabolism disorders by modulating the PI3K/AKT/mTOR signaling pathway

  • Gengxu Li1
  • Xiaoxue Ji1
  • Huilan Gu1
  • Qiyuan Sun1
  • Lu Zhang1
  • Zhenzhen Liu1
  • Zhenguo Qiao2
  • Guodong Zhang3,*,
  • Xuehua Jiao1,*,

1Department of Endocrinology, Suzhou Ninth People's Hospital (Suzhou Ninth Hospital Affiliated to Soochow University), 215200 Suzhou, Jiangsu, China

2Department of Gastroenterology, Suzhou Ninth People's Hospital (Suzhou Ninth Hospital Affiliated to Soochow University), 215200 Suzhou, Jiangsu, China

3Department of Endocrinology, Suzhou Wujiang City Hospital of Traditional Chinese Medicine, 215200 Suzhou, Jiangsu, China

DOI: 10.22514/jomh.2024.160 Vol.20,Issue 9,September 2024 pp.151-157

Submitted: 12 June 2024 Accepted: 16 August 2024

Published: 30 September 2024

*Corresponding Author(s): Guodong Zhang E-mail: gdzhang7823@163.com
*Corresponding Author(s): Xuehua Jiao E-mail: xhjiao7823@163.com

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one abnormal buildup of fat within the liver, independent of excessive alcohol intake. In type 2 diabetes, the presence of NAFLD can exacerbate chronic kidney diseases and mortality in patients. Hepatocyte nuclear factor 1 homeobox A (HNF1A) predominantly expressed in the liver, owns one crucial role in liver development, function and tumorigenesis. However, the precise regulatory role of HNF1A on the progression of type 2 diabetes combined with NAFLD keep dimness. This investigation uncovered that HNF1A levels, both in protein and mRNA expressions, were elevated in high-fat diet plus hyperglycemia (HFG) mice. Furthermore, liver steatosis was strengthened in the HFG group, which was mitigated following the HNF1A inhibition. Knockdown of HNF1A ameliorated glucose and lipid metabolism disorders in HFG mice. Lastly, the study observed an stimulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in HFG mice, but this change was neutralized uponHNF1A silencing. In conclusion, knockdown of HNF1A improved type 2 diabetes combined with NAFLD, as well as disorders in glucose and lipid metabolism, and retarded the PI3K/AKT/mTOR signaling pathway. These finding demonstrated that HNF1A may be one serviceable target for ameliorating type 2 diabetes combined with NAFLD.


Keywords

Type 2 diabetes; HNF1A; Non-alcoholic fatty liver; PI3K/AKT/mTOR pathway


Cite and Share

Gengxu Li,Xiaoxue Ji,Huilan Gu,Qiyuan Sun,Lu Zhang,Zhenzhen Liu,Zhenguo Qiao,Guodong Zhang,Xuehua Jiao. Knockdown of HNF1A improves type 2 diabetes combined with non-alcoholic fatty liver and glucose and lipid metabolism disorders by modulating the PI3K/AKT/mTOR signaling pathway. Journal of Men's Health. 2024. 20(9);151-157.

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