| First Author | Manialawy Y | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 29 | Pages | 9879-9892 |
| PubMed ID | 32439805 | Mgi Jnum | J:297155 |
| Mgi Id | MGI:6466922 | Doi | 10.1074/jbc.RA120.013277 |
| Citation | Manialawy Y, et al. (2020) The magnesium transporter NIPAL1 is a pancreatic islet-expressed protein that conditionally impacts insulin secretion. J Biol Chem 295(29):9879-9892 |
| abstractText | Type 2 diabetes is a chronic metabolic disease characterized by pancreatic beta-cell dysfunction and peripheral insulin resistance. Among individuals with type 2 diabetes, approximately 30% exhibit hypomagnesemia. Hypomagnesemia has been linked to insulin resistance through reduced tyrosine kinase activity of the insulin receptor; however, its impact on pancreatic beta-cell function is unknown. In this study, through analysis of several single-cell RNA-sequencing data sets in tandem with quantitative PCR validation in both murine and human islets, we identified NIPAL1 (NIPA-like domain containing 1), encoding a magnesium influx transporter, as an islet-enriched gene. A series of immunofluorescence experiments confirmed NIPAL1's magnesium-dependent expression and that it specifically localizes to the Golgi in Min6-K8 cells, a pancreatic beta-cell-like cell line (mouse insulinoma 6 clone K8). Under varying magnesium concentrations, NIPAL1 knockdown decreased both basal insulin secretion and total insulin content; in contrast, its overexpression increased total insulin content. Although the expression, distribution, and magnesium responsiveness of NIPAL1 in alpha-TC6 glucagonoma cells (a pancreatic alpha-cell line) were similar to the observations in Min6-K8 cells, no effect was observed on glucagon secretion in alpha-TC6 cells under the conditions studied. Overall, these results suggest that NIPAL1 expression is regulated by extracellular magnesium and that down-regulation of this transporter decreases glucose-stimulated insulin secretion and intracellular insulin content, particularly under conditions of hypomagnesemia. |
