Biology:Zinc transporter 8
 Generic protein structure example |
Zinc transporter 8 (ZNT8) is a protein that in humans is encoded by the SLC30A8 gene.[1] ZNT8 is a zinc transporter related to insulin secretion in humans. In particular, ZNT8 is critical for the accumulation of zinc into beta cell secretory granules and the maintenance of stored insulin as tightly packaged hexamers. Certain alleles of the SLC30A8 gene may increase the risk for developing type 2 diabetes, but a loss-of-function mutation appears to greatly reduce the risk of diabetes.[2]
Clinical significance
Association with type 2 diabetes (T2D)
Twelve rare variants in SLC30A8 have been identified through the sequencing or genotyping of approximately 150,000 individuals from 5 different ancestry groups. SLC30A8 contains a common variant (p.Trp325Arg), which is associated with T2D risk and levels of glucose and proinsulin.[3][4][5] Individuals carrying protein-truncating variants collectively had 65% reduced risk of T2D. Additionally, non-diabetic individuals from Iceland harboring a frameshift variant p. Lys34Serfs*50 demonstrated reduced glucose levels.[2] Earlier functional studies of SLC30A8 suggested that reduced zinc transport increased T2D risk.[6][7] Conversely, loss-of-function mutations in humans indicate that SLC30A8 haploinsufficiency protects against T2D. Therefore, ZnT8 inhibition can serve as a therapeutic strategy in preventing T2D.[2]
See also
References
- ↑ "Entrez Gene: SLC30A8 solute carrier family 30 (zinc transporter), member 8". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=169026.
- ↑ 2.0 2.1 2.2 Flannick, Jason (2014). "Loss-of-function mutations in SLC30A8 protect against type 2 diabetes". Nature Genetics 46 (4): 357–363. doi:10.1038/ng.2915. PMID 24584071.
- ↑ Dupis, J. (Feb 2010). "New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.". Nature Genetics 42 (2): 105–16. doi:10.1038/ng.520. PMID 20081858.
- ↑ Strawbridge, R.J. (October 2011). "Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.". Diabetes 60 (10): 2624–34. doi:10.2337/db11-0415. PMID 21873549. PMC 3178302. http://diabetes.diabetesjournals.org/content/60/10/2624.
- ↑ Morris, A.P. (Sep 2012). "Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.". Nature Genetics 44 (9): 981–90. doi:10.1038/ng.2383. PMID 22885922.
- ↑ Nicolson, T.J. (Sep 2009). "Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes–associated variants.". Diabetes 58 (9): 2070–83. doi:10.2337/db09-0551. PMID 19542200. PMC 2731533. http://diabetes.diabetesjournals.org/content/58/9/2070.
- ↑ Rutter, G.A. (2010). "Think zinc: new roles for zinc in the control of insulin secretion.". Islets 2 (1): 49–50. doi:10.4161/isl.2.1.10259. PMID 21099294.
Further reading
- "ZnT-8, a pancreatic beta-cell-specific zinc transporter.". Biometals 18 (4): 313–7. 2006. doi:10.1007/s10534-005-3687-9. PMID 16158222.
- "DNA cloning using in vitro site-specific recombination.". Genome Res. 10 (11): 1788–95. 2001. doi:10.1101/gr.143000. PMID 11076863.
- "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.". Genome Res. 11 (3): 422–35. 2001. doi:10.1101/gr.GR1547R. PMID 11230166.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters' tissue expression.". BMC Genomics 5 (1): 32. 2004. doi:10.1186/1471-2164-5-32. PMID 15154973.
- "Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules.". Diabetes 53 (9): 2330–7. 2004. doi:10.2337/diabetes.53.9.2330. PMID 15331542.
- "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334.
- "From ORFeome to biology: a functional genomics pipeline.". Genome Res. 14 (10B): 2136–44. 2004. doi:10.1101/gr.2576704. PMID 15489336.
- "The LIFEdb database in 2006.". Nucleic Acids Res. 34 (Database issue): D415–8. 2006. doi:10.1093/nar/gkj139. PMID 16381901.
- "A genome-wide association study identifies novel risk loci for type 2 diabetes.". Nature 445 (7130): 881–5. 2007. doi:10.1038/nature05616. PMID 17293876. Bibcode: 2007Natur.445..881S.
- "The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes.". Proc. Natl. Acad. Sci. U.S.A. 104 (43): 17040–5. 2007. doi:10.1073/pnas.0705894104. PMID 17942684. Bibcode: 2007PNAS..10417040W.
External links
- Type 2 diabetes genes mapped out, BBC News article
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