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<p>Type 2 diabetes mellitus (T2DM) is a major global public health burden. The mechanisms through which glucose-stimulated insulin secretion (GSIS) can be suppressed in individuals with obesity-derived type 2 diabetes mellitus (T2DM) have not been elucidated. Compared to normal subjects, the expression of pigment epithelium-derived factor (PEDF) is upregulated in the islets of patients with obesity and T2DM. However, the role of PEDF in β-cells is unclear. This study employed male PEDF transgenic and knockout mice to assess β-cell function through oral glucose tolerance tests and GSIS assays. Complementary cell line experiments elucidated underlying mechanisms, collectively demonstrating the role of PEDF in regulating insulin secretion. PEDF suppressed GSIS by downregulating the SNARE complex, which suppresses the PI3K/Akt signaling pathway. Thus, targeting PEDF is a potential therapeutic strategy for treating T2DM.</p>

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Elevated PEDF promotes the occurrence of diabetes mellitus via suppressing GSIS by downregulating the SNARE complex

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月25日

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  • Zhen Zhao,
  • Yandan Tan,
  • Jie Fang,
  • Gan Xia,
  • Junchen Li,
  • Qilong Tang,
  • Wanting Xie,
  • Tianxiao Gao,
  • Zhenzhen Fang,
  • Ti Zhou,
  • Xia Yang,
  • Guoquan Gao,
  • Weiwei Qi

摘要

Type 2 diabetes mellitus (T2DM) is a major global public health burden. The mechanisms through which glucose-stimulated insulin secretion (GSIS) can be suppressed in individuals with obesity-derived type 2 diabetes mellitus (T2DM) have not been elucidated. Compared to normal subjects, the expression of pigment epithelium-derived factor (PEDF) is upregulated in the islets of patients with obesity and T2DM. However, the role of PEDF in β-cells is unclear. This study employed male PEDF transgenic and knockout mice to assess β-cell function through oral glucose tolerance tests and GSIS assays. Complementary cell line experiments elucidated underlying mechanisms, collectively demonstrating the role of PEDF in regulating insulin secretion. PEDF suppressed GSIS by downregulating the SNARE complex, which suppresses the PI3K/Akt signaling pathway. Thus, targeting PEDF is a potential therapeutic strategy for treating T2DM.