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Exendin-4 Inhibits TNF-alpha Induced Apoptosis in Insulin-Secreting Cells

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— 1 min read

Researchers at the University of Bari in Italy have investigated the mechanisms of tumor necrosis factor-alpha (TNF-alpha) induced apoptosis and its inhibition by exendin-4 in insulin-secreting cells. The study found that exendin-4 prevents c-Jun N-terminal protein kinase (JNK) activation by TNF-alpha and inhibits TNF-alpha-induced apoptosis in insulin-secreting cells.

Key Takeaways:

  • Exendin-4 prevents TNF-alpha induced JNK activation, reducing apoptosis in insulin-secreting cells by 50%.
  • Treatment with TNF-alpha increased JNK phosphorylation 2-fold, reduced IkappaBalpha protein content by 50%, and induced opposite changes in caspase-3 and Bcl-2 protein content.
  • Exendin-4 also reduced serine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2, increased Akt phosphorylation, and restored caspase-3 and Bcl-2 protein levels to normal.
  • The inhibitory effect of exendin-4 on TNF-alpha-induced JNK phosphorylation was abrogated in the presence of the protein kinase A inhibitor H89.
  • JNK activation mediates TNF-alpha-induced apoptosis and impairment of the IRS/Akt signaling pathway in insulin-secreting cells.
  • Exendin-4 counteracts TNF-alpha-mediated apoptosis and reverses the inhibitory events in the IRS/Akt pathway, resulting in promotion of cell survival.
  • The study was conducted using INS-1 and MIN6 insulinoma cells, as well as isolated pancreatic human islets.

Statistics:

  • 20 ng/ml TNF-alpha was used in the study to induce apoptosis.
  • 10 nm exendin-4 was used to inhibit TNF-alpha-induced apoptosis.
  • 50% reduction in TNF-alpha-induced apoptosis was observed in the presence of exendin-4.
  • 2-fold increase in JNK phosphorylation was observed in response to TNF-alpha.
  • 50% reduction in IkappaBalpha protein content was observed in response to TNF-alpha.
  • 2-fold increase in IRS-2 expression levels was observed in response to exendin-4.

Sources:

  • Endocrinology (Exendin-4 prevents c-Jun N-terminal protein kinase activation by tumor necrosis factor-alpha (TNFalpha) and inhibits TNFalpha-induced apoptosis in insulin-secreting cells)
  • University of Bari
  • A. Natalicchio et al. (no date provided)

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