Betatrophin

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

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

Discovery
The link between betatrophin and mouse 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 is_associated_with::angiopoietin-like gene family and shares extensive homology with Angptl4 and Angptl3, the name Angptl8 is preferred.

Function
Betatrophin is a putative is_associated_with::peptide hormone found in mice that was proposed to increase the rate at which is_associated_with::beta-cells undergo is_associated_with::cell division. Injection of mice with betatrophin cDNA lowered is_associated_with::blood sugar (i.e. hypoglycemia), presumably due to action at the is_associated_with::pancreas. However, treatment of human islets with betatrophin is unable to increase beta-cell division. Furthermore, studies in betatrophin/Angptl8 knock-out mice do not support a role of betatrophin in controlling beta cell growth, yet point to a clear role in regulating plasma triglyceride levels. Based on these studies, it is fairly safe to say that the notion that betatrophin promotes beta cell expansion is dead.

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

In mice betatrophin is secreted by the liver, is_associated_with::white adipose tissue and is_associated_with::brown adipose tissue.

Clinical significance
It was hoped that betatrophin or its homolog in humans may provide an effective treatment for is_associated_with::type 2 diabetes and perhaps even is_associated_with::type I diabetes. Unfortunately, since new data have greatly called into question the ability of betatrophin to increase beta-cell replication, its potential use as a therapy for type 2 diabetes is limited. Inhibition of Angptl8 represents a possible therapeutic strategy for is_associated_with::hypertriglyceridemia.