多肽N-乙酰半乳糖胺转移酶14（GALNT14）在癌症进展和化疗反应中起重要作用。这里,我们发现GALNT14在胰岛β细胞中高表达并调节β细胞的功能和生长。我们发现，在三种啮齿动物2型糖尿病模型的原代胰岛中，Ganlt14的表达水平显着降低。单细胞测序确定Galnt14主要在小鼠胰岛β细胞中表达。Galnt14敲除(G14KO)INS-1细胞系,使用CRISPR/Cas9技术构建的生长正常，但表现出钝的形状，基础胰岛素分泌增加。蛋白质组学和糖蛋白质组学的结合表明，G14KO改变了细胞与细胞的连接，通信,和附着力。胰岛素受体（IR）和IGF1-1R被间接证实为GALNT14底物，G14KO细胞中IGF1诱导的p-AKT水平和细胞生长降低。总的来说,这项研究发现GALNT14是调节β细胞生物学的一种新型调节剂，提供β细胞O-糖基化与糖尿病发展的缺失环节。
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.
