resistin

Structure

Resistin has a uniquemotif of 10 cysteines (C-X11-C-X8- C-X-C-X3-C-X10-C-X-C-X-C-X9-C-C-X3–6-END).Resistin forms multimeric structures (hexamer and trimer) in circulation and their assembly is critical for their function. The crystal structure of resistin reveals an unusual hexameric structure.Each protomer comprises a C-terminal disulfide-rich β-sandwich “head” domain and an N-terminal α-helical “tail” segment. The α-helical segments associate to form three-stranded coils, and surface-exposed interchain disulfide linkages mediate the formation of tail-to-tail hexamers.

Gene, mRNA, and precursor

Thehumanresistingene,RETN, location 19p13.2, consists of four exons.Asplicing variant with excluded Exon 3 exists. Human resistinmRNAhas 327 b that encodes a signal peptide of 16 aa residues and a mature protein of 92 aa residues. The genes encoding resistin and resistin-like peptide (Retnl) have been found in mammals, reptiles, amphibians, and actinistians, but not in birds and fish.

Biological functions

Resistin knockout mice exhibit low blood glucose levels after fasting due to reduced hepatic glucose production. This is partly mediated by the activation of adenosine monophosphate-activated protein kinase (AMPK) and the decreased expression of gluconeogenic enzymes in the liver.Resistin-overexpressing transgenic mice show hepatic insulin resistance and the promotion of phosphoenolpyruvate carboxykinase (PEPCK) in the liver.Resistin-overexpressing rats infected by adenovirus encoding mouse resistin displayed glucose intolerance and hyperinsulinemia.

Clinical implications

Epidemiological studies suggest that resistin is related to insulin resistance and type 2 diabetes mellitus. Several single-nucleotide polymorphisms (SNPs) have been demonstrated to be associated with elevated resistin levels. Polymorphisms in the RETN promoter region are associated with resistin levels in obese Japanese individuals and with an increased risk of coronary disease in a Chinese population. However, this variant in Europeans and Caucasians was found not to be correlated with carotid and coronary atherosclerosis. Increased resistin levels have been observed in patients with rheumatoid arthritis and inflammatory bowel disease.

General Description

Resistin is a cysteine-rich hormone secreted from white adipocytes. Resistin in mice is involved in insulin resistance and links obesity to diabetes while human resistin is involved in inflammation.