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GABA and Artesunate Do Not Induce Pancreatic α-to-β Cell Transdifferentiation In Vivo

Amanda M Ackermann1, Nicholas G Moss2, Klaus H Kaestner3

  • 1Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104, USA.

Cell Metabolism
|July 31, 2018
PubMed

Insights

Activating GABA signaling does not convert pancreatic alpha cells to beta cells. This study questions the potential of GABA signaling agents as a new diabetes therapy, as they did not stimulate cell reprogramming or insulin secretion.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Diabetes Research

Background:

  • Pancreatic alpha cells can potentially be reprogrammed into beta cells.
  • Previous studies suggested GABA signaling activation could induce this transdifferentiation, particularly after beta cell loss.
  • Small molecule-driven alpha-to-beta cell reprogramming offers a potential therapeutic strategy for diabetes.

Purpose of the Study:

  • To rigorously evaluate if activating the GABA signaling pathway induces alpha-to-beta cell transdifferentiation.
  • To assess the therapeutic potential of GABA signaling agents for increasing beta cell mass.

Main Methods:

  • Utilized genetic lineage tracing in Glucagon-CreERT2;Rosa-LSL-eYFP mice.
  • Administered artesunate or GABA long-term to mice.
  • Monitored for alpha-to-beta cell reprogramming and insulin secretion.

Main Results:

  • Long-term treatment with artesunate or GABA did not induce alpha-to-beta cell transdifferentiation.
  • No stimulation of insulin secretion was observed following GABA signaling activation.
  • Findings contradict previous reports on GABA-induced cell reprogramming.

Conclusions:

  • Activation of GABA signaling is not sufficient to reprogram pancreatic alpha cells into beta cells.
  • Artesunate and GABA do not appear to be viable pharmacologic agents for diabetes therapy via cell reprogramming.
  • The efficacy of targeting GABA signaling for diabetes treatment requires further investigation.
Keywords:
artemisinindiabetesislets of Langerhanspancreatic alpha cellpancreatic beta celltransdifferentiation

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