| First Author | Viloria K | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 11 | Pages | 107761 |
| PubMed ID | 32553153 | Mgi Jnum | J:292177 |
| Mgi Id | MGI:6445179 | Doi | 10.1016/j.celrep.2020.107761 |
| Citation | Viloria K, et al. (2020) Vitamin-D-Binding Protein Contributes to the Maintenance of alpha Cell Function and Glucagon Secretion. Cell Rep 31(11):107761 |
| abstractText | Vitamin-D-binding protein (DBP) or group-specific component of serum (GC-globulin) carries vitamin D metabolites from the circulation to target tissues. DBP is highly localized to the liver and pancreatic alpha cells. Although DBP serum levels, gene polymorphisms, and autoantigens have all been associated with diabetes risk, the underlying mechanisms remain unknown. Here, we show that DBP regulates alpha cell morphology, alpha cell function, and glucagon secretion. Deletion of DBP leads to smaller and hyperplastic alpha cells, altered Na(+) channel conductance, impaired alpha cell activation by low glucose, and reduced rates of glucagon secretion both in vivo and in vitro. Mechanistically, this involves reversible changes in islet microfilament abundance and density, as well as changes in glucagon granule distribution. Defects are also seen in beta cell and delta cell function. Immunostaining of human pancreata reveals generalized loss of DBP expression as a feature of late-onset and long-standing, but not early-onset, type 1 diabetes. Thus, DBP regulates alpha cell phenotype, with implications for diabetes pathogenesis. |
