Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article 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, Pitpna 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10352338 | PMC |
| http://dx.doi.org/10.1038/s41467-023-39978-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Oxymatrine attenuates the type 1 diabetes mellitus via negative regulation of the follicular helper T cells.
Eur J Pharmacol
September 2025
Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China. Electronic address:
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder in which autoantibodies cause the immune system to attack and destroy pancreatic β-cells, leading to insufficient insulin production and impaired blood glucose control. T follicular helper (Tfh) cells are recognized as a group of CD4 T cells that help B cells to produce high-affinity antibodies. Our previous research found that oxymatrine (OMT) exhibits excellent immunomodulatory properties on Tfh cells in autoimmune diseases.
View Article and Find Full Text PDFSingle-cell multiome and spatial profiling reveals pancreas cell type-specific gene regulatory programs of type 1 diabetes progression.
Sci Adv
September 2025
Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Cell type-specific regulatory programs that drive type 1 diabetes (T1D) in the pancreas are poorly understood. Here, we performed single-nucleus multiomics and spatial transcriptomics in up to 32 nondiabetic (ND), autoantibody-positive (AAB), and T1D pancreas donors. Genomic profiles from 853,005 cells mapped to 12 pancreatic cell types, including multiple exocrine subtypes.
View Article and Find Full Text PDFClinical Outcomes and Complications of Basal, Bolus, and Combination Insulin Regimens in Type 2 Diabetes Mellitus: Evidence from Published Case Reports.
Diabetes Metab Syndr Obes
September 2025
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia.
Insulin therapy remains a cornerstone in the management of type 2 diabetes mellitus (T2DM), especially in patients experiencing progressive loss of pancreatic beta-cell function or those with inadequate glycemic control despite oral antidiabetic therapy. This review synthesized clinical outcomes from 44 peer-reviewed case reports published between 2019 and 2024, identified through systematic searches in PubMed and Scopus. The included cases involved 15 males and 29 females, with patient ages ranging from 11 to 91 years (mean 53 ± 20.
View Article and Find Full Text PDFMi-Lnc70 Regulates the Progression of Murine Pancreatic β-Cell Line and Affects the Synthesis of Insulin and Glucagon.
Onco Targets Ther
September 2025
State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Science, Inner Mongolia University, Hohhot, 010021, People's Republic of China.
Background: Insulinoma, the most common type of pancreatic endocrine tumor, frequently induces hypoglycemia due to persistent hyperinsulinemia. Although Mi-Lnc70 expression progressively increases during pancreatic maturation in mice, the biological role of Mi-Lnc70 in pancreatic β cells remains elusive.
Aim: This study was designed to investigate the role of LncRNA-Mi-Lnc70 in the mouse pancreatic β-cell line MIN6.
Integrated serum pharmacochemistry, network pharmacology, and experimental validation analyses reveal the active compounds and potential functional mechanism of Tangningtongluo Tablets in treatment of type 2 diabetes mellitus in mice.
J Ethnopharmacol
September 2025
Institute of Materia Medica, Jinzhou Medical University, Jinzhou, Liaoning 121001, China. Electronic address:
Ethnopharmacology Relevance: Tangningtongluo Tablets (TNTL), a novel Miao ethnic medicine for treating type 2 diabetes mellitus (T2DM) and its complications. However, its potential bioactive components and the pharmacological mechanisms underlying its therapeutic effects remain unclear.
Aim Of The Study: This study aims to preliminarily explore the protective effects of TNTL and its active components on pancreatic cells via the PI3K/Akt/FoxO1 pathway and further investigate the underlying mechanisms.