About Visfatin:
Visfatin is a protein present in several mammals, encoded by the NAMPT gene within humans, expressed to a high degree in visceral fat. It is also known as nicotinamide phosphoribosyltransferase, NAmPRTase, NAMPT, pre-B-cell colony-enhancing factor 1, PBEF1, NMN synthetase and NMN pyrophosphorylase. As the primary rate-limited enzyme in the Nicotinamide adenine dinucleotide biosynthesis process, it plays a key role in converting nicotinamide to nicotinomide mononucleotide. As a rather recently discovered protein, it has become known to share a direct relationship with type 2 diabetes, potentially as a marker of predisposition, though this has come under question. There are experimental drugs such as APO866, that inhibits the enzyme, and P7C3 compounds that enhance it for the purposes of combating age-related neurodegeneration
Function
Visfatin is an endocrine, autocrine as well as paracrine peptide with many functions. One includes the part it plays in the nicotinamide adenine dinucleotide biosynthesis process , catalyzing the nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide. It also plays a role in the biosynthesis of nicotinamide dinucleotide. Further functions also include the enhancement of cell proliferation, the process by which the number of cells in increased and the balance kept by mixture of cell death and differentiation, particularly in the promotion of vascular smooth muscle cell maturation and inhibition of neutrophil apoptosis. It also has a function within the hypoglycemic effect, causing insulin within the blood to quickly drop, by lowering blood glucose and improving insulin sensitivity as an insulin receptor activator. It is because of this latter function that it has become known primarily for it’s link to type 2 diabetes, potentially as a genetic marker to help identify those who are predisposed to the condition.
Mechanisms
Though the insulin-mimetic functions of visfatin are under question, there have been proposed links between visfatin levels with several medical conditions. For one, It has anti-apoptotic effects on neutrophils in several models of sepsis. It is also useful as a marker of acute pulmonary lesion. One the other hand, it is diminished in people with steatohepatitis when compared to pure steatosis. Furthermore, increased visfatin levels correlated positively with portal inflammation, bearing a possible association of visfatin with inflammation. Negative correlation of visfatin with creatinine clearance and positive correlation with urinary albumin excretion has been demonstrated, suggesting visfatin circulating levels to be influenced by renal function. An inhibitor of visfatin (FK866) is being tested as a potential anti-tumor agent due to NAD depletion leading to apoptosis on highly metabolically active cells. Visfatin is important to insulin secretion, but its relationship with diabetes risk and progression is still unknown.
Interactions
The interactions of vistatin are still being studied closely, but it has been shown to have a relationship with other adipokines involved in insulin sensitivity, including adiponectin and omentin. There is also possible interaction with iron in gestational diabetes mellitus and interaction with resistin in the risk of colorectal adenoma.
Structure
It has been widely reported by several groups that Visfatin has a crystal structure, with all of them showing that the enztne is a dimeric type II phosphoribosyltransferase enzyme involved in NAD biosynthesis