Fig. 6: Model for the role of rs6048205 in pancreatic differentiation and glycemia homeostasis.

The noncoding SNP rs6048205 risk allele G enhances RXRA binding and activates FOXA2 expression, specifically in the pancreatic progenitor stage. The rs6048205 risk allele G reduces the differentiation efficiency of NKX6-1+ pancreatic progenitor cells, leading to a decrease in functional β cells and an abnormal increase in polyhormonal endocrine cells in vitro. Mice carrying the risk allele G exhibit higher fasting glucose levels and impaired glucose tolerance, contributing to increased susceptibility to diabetes in vivo.