PPARβ/δ affects pancreatic β cell mass and insulin secretion in mice

José Iglesias1, Sebastian Barg, David Vallois

  • 1Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, Lausanne, Switzerland.

Insights

Peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) normally suppresses pancreatic beta cell function. Removing PPARβ/δ increases islet numbers and insulin secretion, impacting metabolic control.

Area of Science:

  • Endocrinology
  • Metabolism
  • Molecular Biology

Background:

  • Peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is known to protect against obesity, dyslipidemia, and insulin resistance.
  • Its specific role in pancreatic beta cell function remains largely uncharacterized.

Purpose of the Study:

  • To investigate the function of PPARβ/δ in pancreatic beta cell biology.
  • To elucidate the impact of PPARβ/δ deletion on beta cell mass and insulin secretion.

Main Methods:

  • Specific deletion of Pparb/d in the epithelial compartment of mouse pancreatic cells.
  • Gene expression profiling of pancreatic beta cells.
  • Analysis of insulin secretion from isolated islets.
  • Assessment of actin cytoskeleton dynamics and protein kinase D activity.

Main Results:

  • Mice with deleted PPARβ/δ exhibited increased islet numbers and hyperinsulinemia.
  • Gene expression analysis revealed PPARβ/δ represses genes involved in vesicular transport and the actin cytoskeleton.
  • PPARβ/δ-deficient islets showed accelerated glucose-stimulated insulin secretion, linked to F-actin disassembly and altered Golgi organization via Protein Kinase D.

Conclusions:

  • PPARβ/δ plays a repressive role in regulating pancreatic beta cell mass and insulin exocytosis.
  • These findings offer new insights into the metabolic actions of PPARβ/δ, particularly concerning glucose homeostasis.

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