GABA treatment does not induce neogenesis of new endocrine cells from pancreatic ductal cells.
Shihao WangXin DongMahan MaaziNan ChenAmar MahilJanel L KoppPublished in: Islets (2023)
Previous studies indicated that ductal cells can contribute to endocrine neogenesis in adult rodents after alpha cells convert into beta cells. This can occur through Pax4 mis-expression in alpha cells or through long-term administration of gamma-aminobutyric acid (GABA) to healthy mice. GABA has also been reported to increase the number of beta cells through direct effects on their proliferation, but only in specific genetic mouse backgrounds. To test whether GABA induces neogenesis of beta cells from ductal cells or affects pancreatic cell proliferation, we administered GABA or saline over 2 or 6 months to Sox9CreER;R26R YFP mice in which 60-80% of large or small ducts were efficiently lineage labeled. We did not observe any increases in islet neogenesis from ductal cells between 1 and 2 months of age in saline treated mice, nor between 2 and 6 months of saline treatment, supporting previous studies indicating that adult ductal cells do not give rise to new endocrine cells during homeostasis. Unlike previous reports, we did not observe an increase in beta cell neogenesis after 2 or 6 months of GABA administration. Nor did we observe a significant increase in the pancreatic islet area, the number of insulin and glucagon double positive cells, or cell proliferation in the pancreas. This indicates that the effect of long term GABA administration on the pancreas is minimal or highly context dependent.
Keyphrases
- induced apoptosis
- cell cycle arrest
- cell proliferation
- oxidative stress
- type diabetes
- emergency department
- young adults
- endoplasmic reticulum stress
- skeletal muscle
- signaling pathway
- cell death
- poor prognosis
- cell therapy
- cell cycle
- transcription factor
- genome wide
- adipose tissue
- copy number
- childhood cancer
- binding protein