Article ; Online: A Novel Intron-Encoded Neuropilin-1 Isoform in Pancreatic Islets Associated With Very Young Age of Onset of Type 1 Diabetes.
2022 Volume 71, Issue 9, Page(s) 2058–2063
Abstract: Net synthesis of pancreatic β-cells peaks before 2 years of life. β-Cell mass is set within the first 5 years of life. In-frame translational readthrough of the NRP1 gene exon 9 into intron 9 generates a truncated neuropilin-1 protein lacking downstream ... ...
| Abstract | Net synthesis of pancreatic β-cells peaks before 2 years of life. β-Cell mass is set within the first 5 years of life. In-frame translational readthrough of the NRP1 gene exon 9 into intron 9 generates a truncated neuropilin-1 protein lacking downstream sequence necessary for binding VEGF that stimulates β-cell replication. VEGF is critical for developing but not adult islet neogenesis. Herein we show that cells in human pancreatic islets containing the full-length neuropilin-1 possess insulin but cells that contain the truncated neuropilin-1 are devoid of insulin. Decreased insulin cells increases susceptibility to onset of type 1 diabetes at a younger age. We also show that the frequency of a genetic marker in NRP1 intron 9 is higher among patients with onset of type 1 diabetes before age 4 years (31.8%), including those with onset at 0.67-2.00 and 2-4 years, compared with that in patients with onset at 4-8 years, at 8-12 years, and after 16 years (16.1%) with frequency equal to that in subjects without diabetes (16.0%). Decreased insulin cells plus the genetic data are consistent with a low effect mechanism that alters the onset of type 1 diabetes to a very young age in some patients, thus supporting the endotype concept that type 1 diabetes is a heterogeneous disease. |
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| MeSH term(s) | Age of Onset ; Child, Preschool ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/metabolism ; Humans ; Insulin/metabolism ; Introns/genetics ; Islets of Langerhans/metabolism ; Neuropilin-1/genetics ; Neuropilin-1/metabolism ; Protein Isoforms/genetics ; Vascular Endothelial Growth Factor A/metabolism | |||||
| Chemical Substances | Insulin ; Protein Isoforms ; Vascular Endothelial Growth Factor A ; Neuropilin-1 (144713-63-3) | |||||
| Language | English | |||||
| Publishing date | 2022-06-17 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 80085-5 | |||||
| ISSN | 1939-327X ; 0012-1797 | |||||
| ISSN (online) | 1939-327X | |||||
| ISSN | 0012-1797 | |||||
| DOI | 10.2337/db21-1070 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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