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High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds
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The long non-coding RNA KDM4A-AS1 protects β-cell function via the miR-423-5p/growth differentiation factor 11 axis

Yan Zeng1, Liyu Sun2, Junli Li3

  • 1Laboratory Department, Ganzhou Women and Children's Health Care Hospital, Ganzhou, China.

Diabetic Medicine : a Journal of the British Diabetic Association
|April 3, 2026
PubMed
Abstract

Insights

Long non-coding RNA KDM4A-AS1 protects pancreatic beta cells in type 2 diabetes by regulating the miR-423-5p/GDF11 pathway. This finding offers a novel diagnostic and therapeutic target for type 2 diabetes mellitus (T2DM).

Area of Science:

  • Molecular Biology
  • Endocrinology
  • Genetics

Background:

  • Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder with severe health complications.
  • Long non-coding RNAs (lncRNAs) play a role in the pathogenesis of diabetes and its associated conditions.

Purpose of the Study:

  • To investigate the regulatory mechanism of lncRNA KDM4A-AS1 in T2DM.
  • To elucidate the role of KDM4A-AS1 in pancreatic beta cell function.

Main Methods:

  • Serum samples from 98 T2DM patients and 91 healthy controls were analyzed for gene expression using RT-qPCR.
  • In vitro studies assessed cell proliferation (CCK-8), apoptosis (flow cytometry), and insulin secretion (ELISA).
  • RNA immunoprecipitation and dual-luciferase reporter assays confirmed interactions between KDM4A-AS1, miR-423-5p, and GDF11.

Main Results:

  • KDM4A-AS1 and GDF11 were downregulated, while miR-423-5p was upregulated in T2DM patients' serum.
  • KDM4A-AS1 levels correlated negatively with fasting plasma glucose and HbA1c, indicating diagnostic potential for T2DM.
  • Overexpression of KDM4A-AS1 promoted insulin gene expression, enhanced glucose-stimulated insulin secretion, increased beta cell proliferation, and reduced apoptosis.

Conclusions:

  • KDM4A-AS1 protects pancreatic beta cell function via the miR-423-5p/GDF11 signaling axis.
  • KDM4A-AS1 represents a promising new target for T2DM diagnosis and treatment.
Keywords:
GDF11KDM4A‐AS1miR‐423‐5ppancreatic β celltype 2 diabetes mellitus

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