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Growth differentiation factor-15 prevents glucotoxicity and connexin-36 downregulation in pancreatic beta-cells

Mohamed Asrih1, Rodolphe Dusaulcy1, Yvan Gosmain1

  • 1Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland; University of Geneva Medical School, 1211, Geneva, Switzerland.

Molecular and Cellular Endocrinology
|November 11, 2021
PubMed

Insights

Growth differentiation factor 15 (GDF15) protects pancreatic beta-cells from dying under diabetic conditions. Endogenous GDF15 is crucial for beta-cell survival, but not insulin secretion, when exposed to high glucose and fat.

Area of Science:

  • Endocrinology
  • Metabolic Research
  • Cell Biology

Background:

  • Pancreatic beta cell dysfunction is central to type 2 diabetes.
  • Growth differentiation factor 15 (GDF15) is an energy homeostasis regulator with known metabolic benefits.
  • The specific role of GDF15 in pancreatic beta-cell function and survival is not well understood.

Purpose of the Study:

  • To investigate the effects of GDF15 on pancreatic beta-cell insulin secretion and viability.
  • To elucidate the role of endogenous GDF15 in beta-cell function under normal and diabetogenic conditions.

Main Methods:

  • Experiments utilized cell models and histological sections from wild-type and GDF15 knockout mice.
  • Bioinformatics analysis was performed to identify GDF15-correlated genes.
  • Assessed glucose-stimulated insulin secretion (GSIS) and cell viability under varying conditions, including glucolipotoxicity.

Main Results:

  • GDF15 was found to prevent altered GSIS and connexin-36 downregulation caused by glucotoxicity.
  • Inhibition of endogenous GDF15 reduced GSIS under standard conditions.
  • Inhibition of endogenous GDF15 exacerbated cell death under glucolipotoxic conditions, but did not affect GSIS.

Conclusions:

  • Endogenous GDF15 plays a vital role in pancreatic beta-cell survival, particularly under glucolipotoxic stress.
  • GDF15 is not essential for GSIS in beta-cells under glucolipotoxic conditions.
  • GDF15 may be a therapeutic target for preserving beta-cell function in type 2 diabetes.
Keywords:
Connexin-36GDF15GlucotoxicityINS-1EPancreatic beta-cell dysfunction

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