Betatrophin Mouse ELISA

Features

• It is intended for research use only
• The total assay time is less than 3.5 hours
• The kit measures betatrophin in serum
• Assay format is 96 wells
• Standard is recombinant protein based
• Components of the kit are provided ready to use, concentrated or lyophilized

Research topic

Diabetology - Other Relevant Products, Energy metabolism and body weight regulation, Lipoprotein metabolism

Summary

Betatrophin belongs to the family of angiopoietin-like proteins and it has been given many different names: angiopoietin-like protein-8 (ANGPTL8), lipasin, hepatocellular carcinoma-associated protein-TD26, RIFL, and most recently, betatrophin.
The ANGPTL protein family contains 7 typical members which are characterized by the presence of a coiled-coil domain at the N-terminus, a fibrinogen-like domain at the C-terminus and a signal peptide for protein secretion. N- and C-terminal domains of ANGPTLs have distinct functions (lipid regulation, angiogenesis). Betatrophin is a new but atypical member of the ANGPTL family, because it lacks the fibrinogen-like domain.
The gene for mouse betatrophin encodes a protein composed of 198 amino acids (the mouse gene is annotated as Gm6484; the human gene is annotated as C19orf80). The gene Gm6484 has four exons and lies within the intron of another gene, Dock6, on the opposite strand. The mouse gene for betatrophin lies on mouse chromosome 9 and the human gene for betatrophin lies on human chromosome 19. Betatrophin is a small protein with a molecular weight of 22 kDa.
Betatrophin is highly conserved in all mammalian species examined but is evidently absent in nonmammalian vertebrates and in invertebrates.
Expression of betatrophin in mice has been described in several organs including the liver, brown and white adipose tissue, adrenal glands, duodenum and small intestine. In humans, betatrophin is primarily expressed in the liver, where betatrophin mRNA levels are 250-fold higher than in other tissues.
The hormone betatrophin was recently described as a potent stimulator of beta cell proliferation in mice. Transient expression of betatrophin in mouse liver significantly and specifically promotes pancreatic β-cell proliferation, expands β-cell mass, and improves glucose tolerance. Induced insulin resistance is a known potent stimulator of betatrophin expression in liver and fat tissue. The basic proliferation rate of β-cells in adult mammals is very low under normal physiological conditions, typically less than 1%. However, when metabolically challenged, such as during pregnancy, diet-induced insulin resistance, and experimental β-cell ablation, β-cells have the capacity to expand by proliferation, at least in rodents. About 20-fold surge in hepatic expression of betatrophin mRNA was seen in mice during gestation, a time known to be associated with insulin resistance, accompanied with pancreatic β-cell expansion. In particular, hepatic insulin resistance was shown to be a powerful promoter of β-cell replication in mice decades ago. However, the mechanism of action of betatrophin remains unknown.
ANGPTL8 (betatrophin) is involved in lipid metabolism. ANGPTL8 plays a major role in the trafficking of triglycerides to peripheral tissues in response to food intake in mice.
The secreted protein has been detected in human plasma. Plasma betatrophin concentrations are approximately doubled in patients with type 1 diabetes. Betatrophin is 40% higher in patients with type 2 diabetes and levels increase with age.
The recent discovery of betatrophin has raised high hopes for the rapid development of a novel therapeutic approach for the treatment of diabetes. At present, however, the effects of betatrophin on human β-cells are not known. Although mouse β-cells, in their normal location in the pancreas or when transplanted under the kidney capsule, respond with a dramatic increase in β-cell DNA replication, human β-cells are completely unresponsive. These results put into question whether betatrophin could be useful with respect to treating human diabetes.