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Liraglutide prevents β-cell apoptosis via inactivation of NOX2 and its related signaling pathway

Min Ding1, Qian-Hua Fang1, Yuan-Tao Cui1

  • 1NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin 300070, PR China.

Journal of Diabetes and Its Complications
|February 18, 2019
PubMed
Abstract

Insights

Liraglutide treatment reduced pancreatic beta-cell apoptosis in diabetic rats by targeting the p-AMPKα/NOX2/JNK1/2 pathway. This suggests glucagon-like peptide-1 receptor agonists (GLP-1RAs) are promising for diabetes mellitus treatment.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Pharmacology

Background:

  • High glucose (HG) induces pancreatic beta-cell apoptosis, a key factor in diabetes mellitus (DM) progression.
  • NADPH oxidase (NOX2) plays a critical role in beta-cell apoptosis.
  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are being investigated for their therapeutic potential in DM.

Purpose of the Study:

  • To assess the effect of liraglutide, a GLP-1RA, on pancreatic beta-cell apoptosis in diabetic models.
  • To elucidate the underlying molecular mechanisms of liraglutide's action.

Main Methods:

  • Diabetic rat models (STZ+HFD) were treated with liraglutide for 12 weeks.
  • In vivo beta-cell function was assessed using hyperglycemic clamp tests.
  • In vitro apoptosis rates and reactive oxygen species (ROS) levels were measured using flow cytometry and DCFH-DA assay, respectively.

Main Results:

  • Liraglutide significantly improved islet function and morphology and reduced beta-cell apoptosis in diabetic rats.
  • Liraglutide treatment decreased Thr183/Thr185 p-JNK1/2 and NOX2 levels.
  • Liraglutide upregulated p-AMPKα, inhibiting NOX2 activation and mitigating HG-induced beta-cell apoptosis.

Conclusions:

  • The p-AMPKα/NOX2/JNK1/2 pathway is crucial for liraglutide's anti-apoptotic effects in beta-cells.
  • GLP-1RAs, like liraglutide, show promise as therapeutic agents for diabetes mellitus.
Keywords:
ApoptosisGLP-1LiraglutideNOX2β-Cells

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