Targeting PFKFB3 to restore glucose metabolism in acute pancreatitis via nanovesicle delivery

Mol Med. 2025 Jul 5;31(1):253. doi: 10.1186/s10020-025-01261-y.

Abstract

Background: Acute pancreatitis (AP) is a severe inflammatory disease frequently accompanied by disturbances in glucose metabolism, which further complicate the disease prognosis. This study aims to explore the role of PFKFB3, a key glycolytic enzyme, in regulating glucose metabolism in AP and assess the potential of PFKFB3 inhibition via nanovesicle delivery to mitigate metabolic dysfunction.

Methods: Transcriptomic data from Gene Expression Omnibus (GEO), including single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing, were analyzed to investigate the molecular mechanisms involved in glucose metabolism dysregulation in AP. The therapeutic effects of PFKFB3 inhibition via nanovesicle-based delivery were evaluated using both in vivo and in vitro AP models.

Results: PFKFB3 inhibition significantly restored normal glycolytic function and improved glucose metabolism in AP models. Moreover, nanovesicle-mediated delivery also alleviated both inflammation and metabolic disturbances, highlighting its promise as a therapeutic strategy for managing glucose dysfunction in AP.

Conclusion: Our findings identify PFKFB3 as a critical therapeutic target for treating glucose metabolism disorders in acute pancreatitis. Nanovesicle-based PFKFB3 inhibition may serve as an innovative approach to address metabolic complications associated with AP, offering a new direction for therapeutic interventions in inflammatory diseases.

Keywords: Acute pancreatitis; Glucose metabolism disorder; Machine learning; Nanovesicles; PFKFB3 inhibitor; Single-cell RNA sequencing.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Glucose* / metabolism
  • Glycolysis / drug effects
  • Humans
  • Male
  • Mice
  • Pancreatitis* / drug therapy
  • Pancreatitis* / etiology
  • Pancreatitis* / metabolism
  • Pancreatitis* / pathology
  • Phosphofructokinase-2* / antagonists & inhibitors
  • Phosphofructokinase-2* / genetics
  • Phosphofructokinase-2* / metabolism

Substances

  • Phosphofructokinase-2
  • Glucose
  • PFKFB3 protein, human
  • PFKFB3 protein, mouse

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