The amylin superfamily: a novel grouping of biologically active polypeptides related to the insulin A-chain.
The peptide amylin (previously termed Diabetes Associated Peptide) has recently been isolated and characterised from the amyloid of the pancreatic islets of Langerhans from human type 2 diabetics. Amylin shows about 46% identity in amino acid sequence on comparison with the calcitonin gene-related peptides (CGRPs) and also shows some similarity to insulin. Recent studies have also shown that both amylin and CGRP are potent inhibitors of insulin-stimulated glycogen synthesis in skeletal muscle in vitro. Hormones may be arranged into families, therefore a degree of order exists even though hormone-mediated effects are complex. The polypeptides insulin, insulin-like growth factors (IGFs) and relaxins have been grouped into such a family with similarities both at the protein-structural and genetic levels. We now demonstrate that this insulin-related family, along with amylin and the CGRPs, are members of a peptide superfamily defined by structural similarity in the region corresponding to the A-chain of insulin. In order to distinguish this grouping of small biologically active peptides from the previous one, we have designated it the amylin superfamily. All the members of the previously defined insulin family have a region homologous to the insulin B-chain. Insulin, the IGFs, the relaxins, the CGRPs and amylin are all involved in carbohydrate metabolism and therefore these peptides are functionally as well as structurally related. This grouping of peptides may have important implications for the study of human metabolic disease.
Cooper
G J
GJ
Department of Biochemistry, University of Oxford, U.K.
Leighton
B
B
Willis
A C
AC
Day
A J
AJ
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000235:genetics; D058228:Islet Amyloid Polypeptide; D008969:Molecular Sequence Data
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D015740:Calcitonin Gene-Related Peptide