描述:
Resistin (resistance-to-insulin), also known as adipocyte-specific secretory factor (ADSF)
and found in inflammatory zone 3 (FIZZ3), is a 10 kDa member of a small family of secreted
cysteine-rich peptide hormones. These molecules purportedly play some role in inflammation,
glucose metabolism, and angiogenesis. Human Resistin precursor is 108 amino acids (aa) in
length. It contains an 18 aa signal sequence plus a 90 aa mature region. The mature region
shows an N-terminal α-helical tail (aa 23 - 44) and a C-terminal β-sheet globular head
(aa 47 - 108). The Resistin molecule circulates as either a noncovalent trimer (minor form), or
a disulfidelinked homohexamer (major form). Noncovalent trimers are generated when the
αhelical segments self-associate to form a threestranded coiledcoil structure. Covalent
hexamers subsequently appear when the free Cys at position # 26 is engaged by adjacent
trimers. It is hypothesized that the hexamer is the inactive form of the molecule, and bioactivity
is achieved at the target site by disulfide bond reduction. Although Resistin family molecules
can noncovalently interact to form heterotrimers in vitro, there is no evidence to suggest this
occurs in vivo with Resistin. Mature human Resistin shares 56% and 54% aa identity with mouse
and rat Resistin, respectively. Rat Resistin possesses an alternate start site at Met48; this Met is
not found in the mouse molecule, however . Rodent Resistin is expressed by white adipocytes,
splenocytes, astrocytes, and anterior pituitary epithelium. Although the function of Resistin is
unclear, it would seem to block insulinstimulated uptake of glucose by adipocytes and promote
glucose release by hepatocytes. As such, it has been proposed to participate in diet-induced
insulinsensitivity. Diets high in fat promote an increase in overall adipocyte size. Hypertrophic
adipocytes are known to secrete TNF-α which acts locally to block ACRP30 production. Since
ACRP30 is an insulinsensitizer, a drop in ACRP30 availability leads to insulininsensitivity, which
drives increased insulin production (a compensatory mechanism). High insulin induces Resistin
secretion which now antagonizes insulin action, prompting more insulin production and more
Resistin secretion.
原厂资料:
Resistin (resistance-to-insulin), also known as adipocyte-specific secretory factor (ADSF)
and found in inflammatory zone 3 (FIZZ3), is a 10 kDa member of a small family of secreted
cysteine-rich peptide hormones. These molecules purportedly play some role in inflammation,
glucose metabolism, and angiogenesis. Human Resistin precursor is 108 amino acids (aa) in
length. It contains an 18 aa signal sequence plus a 90 aa mature region. The mature region
shows an N-terminal α-helical tail (aa 23 - 44) and a C-terminal β-sheet globular head
(aa 47 - 108). The Resistin molecule circulates as either a noncovalent trimer (minor form), or
a disulfidelinked homohexamer (major form). Noncovalent trimers are generated when the
αhelical segments self-associate to form a threestranded coiledcoil structure. Covalent
hexamers subsequently appear when the free Cys at position # 26 is engaged by adjacent
trimers. It is hypothesized that the hexamer is the inactive form of the molecule, and bioactivity
is achieved at the target site by disulfide bond reduction. Although Resistin family molecules
can noncovalently interact to form heterotrimers in vitro, there is no evidence to suggest this
occurs in vivo with Resistin. Mature human Resistin shares 56% and 54% aa identity with mouse
and rat Resistin, respectively. Rat Resistin possesses an alternate start site at Met48; this Met is
not found in the mouse molecule, however . Rodent Resistin is expressed by white adipocytes,
splenocytes, astrocytes, and anterior pituitary epithelium. Although the function of Resistin is
unclear, it would seem to block insulinstimulated uptake of glucose by adipocytes and promote
glucose release by hepatocytes. As such, it has been proposed to participate in diet-induced
insulinsensitivity. Diets high in fat promote an increase in overall adipocyte size. Hypertrophic
adipocytes are known to secrete TNF-α which acts locally to block ACRP30 production. Since
ACRP30 is an insulinsensitizer, a drop in ACRP30 availability leads to insulininsensitivity, which
drives increased insulin production (a compensatory mechanism). High insulin induces Resistin
secretion which now antagonizes insulin action, prompting more insulin production and more
Resistin secretion.