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Identification and analysis of type 2 diabetes-mellitus-associated autophagy-related genes

Kun Cui1, Zhizheng Li2

  • 1Respiratory Medicine, Tangshan Gongren Hospital, Tangshan, Hebei, China.

Frontiers in Endocrinology
|May 24, 2023
PubMed
Abstract

Insights

Autophagy is crucial for pancreatic beta cell survival and type 2 diabetes. This study identifies key autophagy-related genes as potential biomarkers and therapeutic targets for T2DM treatment.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Genetics

Background:

  • Autophagy is a cellular process vital for protecting against harmful agents and is implicated in pancreatic beta cell survival.
  • Dysregulation of autophagy is linked to the development of type 2 diabetes mellitus (T2DM).
  • Autophagy-related genes (ARGs) are potential biomarkers for T2DM treatment strategies.

Purpose of the Study:

  • To identify differentially expressed autophagy-related genes (DEARGs) in T2DM.
  • To investigate the role of specific DEARGs in pancreatic beta cell function.
  • To explore potential therapeutic targets for T2DM based on ARG expression.

Main Methods:

  • Downloaded and analyzed the GSE25724 dataset from the Gene Expression Omnibus (GEO) database.
  • Identified DEARGs by intersecting ARGs with differentially expressed genes (DEGs) in T2DM islet samples.
  • Constructed a protein-protein interaction (PPI) network to identify hub DEARGs and validated their expression using qRT-PCR in human and rat islet cells.

Main Results:

  • Identified 1,270 DEGs and 30 DEARGs enriched in autophagy and mitophagy pathways.
  • Discovered ten hub ARGs, including EIF2AK3, RB1CC1, HSPA5, LAMP2, and GABARAPL2, with validated differential expression in islet cells.
  • Overexpression of EIF2AK3 or RB1CC1 enhanced islet cell viability and insulin secretion.

Conclusions:

  • This research identifies novel DEARGs as potential biomarkers for T2DM.
  • The study highlights EIF2AK3 and RB1CC1 as promising therapeutic targets for T2DM.
  • Findings contribute to understanding autophagy's role in T2DM pathogenesis and treatment.
Keywords:
autophagybiomarkerdifferentially expressed geneshub genestype 2 diabetes mellitus

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