PLX191450

GSE58025: Aldh1b1 controlled timing of pancreas specification is important for cell functionality and glucose homeostasis in the adult.

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Maintenance of normal glucose homeostasis is disturbed in diabetes. In the cell, this involves a glucose sensor converting increased glucose levels to insulin secretion. Understanding the developmental regulatory networks that define a fully functional cell is important for elucidating the genetic origins of the disease and deriving mature cells for therapy.; Here we show that Aldh1b1 regulates the timing of differentiation in the developing pancreas and the patterning of cells. In its absence, expression of key cell transcription factors is deregulated at birth. Null animals become glucose intolerant and hyperglycemic with age. Beta cell dysfunction is associated with extensive transcripteome changes, increased oxidative stress, energy depletion and defects in both glucose sensing and stimulus coupling secretion. These findings identify Aldh1b1 as a central regulator of the transition from the pancreas endocrine progenitor to the committed cell and demonstrate that changes in the timing of this transition manifest much later in adult life with cell dysfunction. SOURCE: Anthony Gavalas PLID