ARTICLE: Restoration of PITPNA in Type 2 diabetic human islets reverses pancreatic beta-cell dysfunction
AUTHORS: Yu-Te Yeh, Chandan Sona, Xin Yan, Yunxiao Li, Adrija Pathak, Mark I McDermott, Zhigang Xie, Liangwen Liu, Anoop Arunagiri, Yuting Wang, Amaury Cazenave-Gassiot, Adhideb Ghosh, Ferdinand von Meyenn, Sivarajan Kumarasamy, Sonia M Najjar, Shiqi Jia, Markus R Wenk, Alexis Traynor-Kaplan 15, Peter Arvan, Sebastian Barg, Vytas A Bankaitis, Matthew N Poy
JOURNAL: Nat Commun. 2023 Jul 17;14(1):4250. doi: 10.1038/s41467-023-39978-1.
Abstract
Defects in insulin processing and granule maturation are linked to pancreatic beta-cell failure during type 2 diabetes (T2D). Phosphatidylinositol transfer protein alpha (PITPNA) stimulates activity of phosphatidylinositol (PtdIns) 4-OH kinase to produce sufficient PtdIns-4-phosphate (PtdIns-4-P) in the trans-Golgi network to promote insulin granule maturation. PITPNA in beta-cells of T2D human subjects is markedly reduced suggesting its depletion accompanies beta-cell dysfunction. Conditional deletion of Pitpna in the beta-cells of Ins-Cre, Pitpnaflox/flox mice leads to hyperglycemia resulting from decreasing glucose-stimulated insulin secretion (GSIS) and reducing pancreatic beta-cell mass. Furthermore, PITPNA silencing in human islets confirms its role in PtdIns-4-P synthesis and leads to impaired insulin granule maturation and docking, GSIS, and proinsulin processing with evidence of ER stress. Restoration of PITPNA in islets of T2D human subjects reverses these beta-cell defects and identify PITPNA as a critical target linked to beta-cell failure in T2D.
For the full article, click here.
For a link to the abstract, click here.
