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Activation of a Yap1-mesenchymal-like program in β-cells during diabetes

Wendy M McKimpson1, Nehan Hoque2, Matthew Barter3

  • 1Department of Medicine, Division of Endocrinology, Columbia University, New York, NY, USA; Naomi Berrie Diabetes Center, Columbia University, New York, NY, USA; Department of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA, USA.

Cell Reports
|June 30, 2026
PubMed

Insights

Type 2 diabetes involves beta-cell failure. Researchers found that the Yap1 protein triggers an EMT-like program in beta cells, leading to their loss and driving diabetes progression.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Metabolic Diseases

Background:

  • Type 2 diabetes is characterized by beta-cell dysfunction and loss.
  • The underlying signaling pathways driving beta-cell failure are not fully understood.

Purpose of the Study:

  • To identify the signaling pathways responsible for beta-cell loss in type 2 diabetes.
  • To investigate the role of the Yap1 transcription factor in beta-cell failure.

Main Methods:

  • Investigated Yap1 expression in human and mouse beta cells under diabetic conditions.
  • Utilized chemical inhibition and overexpression of Yap1 in isolated islets and mouse models.
  • Assessed changes in epithelial-to-mesenchymal (EMT)-like markers (e.g., vimentin) and insulin secretion.

Main Results:

  • Yap1 is upregulated in beta cells in response to oxidative stress and mitochondrial dysfunction.
  • Yap1 activation initiates an EMT-like program in beta cells, leading to vimentin expression.
  • Inhibition of Yap1 reversed EMT-like changes, improved insulin secretion, and alleviated diabetes in mice.

Conclusions:

  • Yap1 acts as a critical initiator of beta-cell loss via an EMT-like program in type 2 diabetes.
  • Targeting Yap1 represents a potential therapeutic strategy for treating type 2 diabetes.
Keywords:
CP: developmental biologyCP: metabolismN-cadherinSnailVimentinYap1beta-cell failurediabetesepithelial-to-mesenchymal transitionextracellular matrixmitochondrial dysfunctionpancreatic β-cell

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