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miR-4431 targets TRIP10/PRKD1 and impairs glucose metabolism

Chongge Pan1, Menghuan Li2, Jingzhou Wang1

  • 1Department of Biochemistry and Molecular Biology, Shihezi University School of Medicine, Shihezi, China.

Journal of Diabetes Investigation
|November 20, 2021
PubMed
Abstract

Insights

Obesity and type 2 diabetes are linked to elevated miR-4431 levels. This microRNA targets TRIP10/PRKD1, impairing glucose metabolism and insulin sensitivity in obesity.

Area of Science:

  • Metabolic disease research
  • Molecular biology
  • Endocrinology

Background:

  • Obesity is a major risk factor for metabolic disorders, particularly type 2 diabetes mellitus.
  • MicroRNAs (miRNAs) are implicated in the pathogenesis of type 2 diabetes mellitus.

Purpose of the Study:

  • To investigate the role of miR-4431 in obesity-associated type 2 diabetes mellitus.
  • To explore the molecular mechanisms underlying miR-4431's function in metabolic regulation.

Main Methods:

  • Serum miR-4431 levels were analyzed in normal, obese, and type 2 diabetes mellitus individuals.
  • miR-4431 mimic or sponge was administered to high-fat diet (HFD) mice to assess glucose tolerance, insulin sensitivity, and lipid profiles.
  • Bioinformatics and in vitro assays were used to identify and validate miR-4431's downstream targets.

Main Results:

  • Serum miR-4431 levels were significantly elevated in obese and type 2 diabetes mellitus subjects, correlating with BMI and fasting glucose.
  • HFD mice exhibited increased miR-4431 levels, leading to impaired glucose tolerance, insulin sensitivity, and dysregulated lipid metabolism.
  • miR-4431 was found to downregulate TRIP10 and PRKD1 mRNA and protein levels, inhibiting glucose uptake in liver cells.

Conclusions:

  • miR-4431 directly targets TRIP10 and PRKD1.
  • miR-4431 plays a critical role in impairing glucose metabolism and exacerbating obesity-related type 2 diabetes mellitus.
  • Targeting miR-4431 may offer a therapeutic strategy for metabolic disorders associated with obesity.
Keywords:
Glucose metabolismType 2 diabetes mellitusmiR-4431

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