Betatrophin

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Chromosome 19 open reading frame 80
Identifiers
Symbols C19orf80 ; ANGPTL8; PRO1185; PVPA599; RIFL; TD26
External IDs HomoloGene83285 GeneCards: C19orf80 Gene
Orthologs
Species Human Mouse
Entrez 55908 624219
Ensembl ENSG00000130173 ENSMUSG00000047822
UniProt Q6UXH0 Q8R1L8
RefSeq (mRNA) NM_018687 NM_001080940
RefSeq (protein) NP_061157 NP_001074409
Location (UCSC) Chr 19:
11.35 – 11.35 Mb
Chr 9:
21.84 – 21.84 Mb
PubMed search [1] [2]

Betatrophin is a protein that in humans is encoded by the C19orf80 gene.

Gene[edit]

The gene for betatrophin lies on mouse chromosome 9 (gene symbol: Gm6484) and on human chromosome 19 (gene symbol: C19orf80).

Discovery[edit]

The link between betatrophin and islet cell proliferation was made by Douglas Melton and Peng Yi from Harvard in 2013. Before that time, betatrophin was and actually still is known under various names: TD26, RIFL, Lipasin, and Angptl8. Since betatrophin is a member of the angiopoietin-like gene family and shares extensive homology with Angptl4 and Angptl3, the name Angptl8 is preferred.

Function[edit]

Betatrophin is a putative peptide hormone found in mice that increases the rate at which beta-cells undergo cell division. Injection of mice with betatrophin cDNA lowered blood sugar (i.e. hypoglycemia), presumably due to action at the pancreas.

The encoded 22kDa protein contains an N-terminal secretion signal and two coiled-coil domains and is a member of the angiopoietin-like gene family. However, in contrast to other angiopoietin-like proteins, betatrophin lacks the C-terminal fibrinogen-like domain. It shares with Angptl4 and Angptl3 the ability to inhibit the enzyme Lipoprotein lipase, causing elevation of circulating Triglyceride levels in mice. Despite having elevated post-heparin plasma Lipoprotein lipase activity, mice lacking betatrophin/Angptl8 exhibit markedly decreased uptake of Very low-density lipoprotein-derived fatty acids into adipose tissue.[1] Deletion of betatrophin/Angptl8 does not seem to impact glucose and insulin tolerance in mice.[1]

In mice betatrophin is secreted by the liver, white adipose tissue and brown adipose tissue.[2][3]

Clinical significance[edit]

It is hoped that betatrophin or its homolog in humans may provide an effective treatment for type II diabetes and perhaps even type I diabetes.[4]

References[edit]

  1. ^ a b Wang Y, Quagliarini F, Gusarova V, Gromada J, Valenzuela DM, Cohen JC, Hobbs HH (October 2013). "Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis.". Proc Natl Acad Sci U S A 110 (10): 16109–14. doi:10.1073/pnas.1315292110. PMID 24043787. 
  2. ^ Ren G, Kim JY, Smas CM. (August 2012). "Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism.". Am J Physiol Endocrinol Metab 303 (3): E334. doi:10.1152/ajpendo.00084.2012. PMID 22569073. 
  3. ^ Zhang R (August 2012). "Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels.". Biochem Biophys Res Commun. 424 (4): 786–92. doi:10.1016/j.bbrc.2012.07.038. PMID 22809513. 
  4. ^ Yi P, Park JS, Melton DA (April 2013). "Betatrophin: A Hormone that Controls Pancreatic β Cell Proliferation". Cell 153 (4): 747–58. doi:10.1016/j.cell.2013.04.008. PMC 3756510. PMID 23623304.