%0 Journal Article
%T Polypeptide N-Acetylgalactosaminyl transferase 14 is a novel mediator in pancreatic β-cell function and growth.
%A Shu T
%A Zhang Y
%A Sun T
%A Zhu Y
%J Mol Cell Endocrinol
%V 591
%N 0
%D 2024 Sep 15
%M 38763428
%F 4.369
%R 10.1016/j.mce.2024.112269
%X Polypeptide N-Acetylgalactosaminyl transferase 14 (GALNT14) plays important roles in cancer progression and chemotherapy response. Here, we show that GALNT14 is highly expressed in pancreatic β cells and regulates β cell function and growth. We found that the expression level of Ganlt14 was significantly decreased in the primary islets from three rodent type-2 diabetic models. Single-Cell sequencing defined that Galnt14 was mainly expressed in β cells of mouse islets. Galnt14 knockout (G14KO) INS-1 cell line, constructed by using CRISPR/Cas9 technology were growth normal, but showed blunt shape, and increased basal insulin secretion. Combined proteomics and glycoproteomics demonstrated that G14KO altered cell-to-cell junctions, communication, and adhesion. Insulin receptor (IR) and IGF1-1R were indirectly confirmed for GALNT14 substrates, contributed to diminished IGF1-induced p-AKT levels and cell growth in G14KO cells. Overall, this study uncovers that GALNT14 is a novel modulator in regulating β cells biology, providing a missing link of β cells O-glycosylation to diabetes development.