Biology:Zinc transporter 8

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Short description: Protein found in humans


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
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

  1. "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. 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. 
  3. 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. 
  4. 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. 
  5. 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. 
  6. 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. 
  7. 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

External links