Usage And Synthesis
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.
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.
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.
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.
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