Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients.
Deposition of amyloid in pancreatic islets is a common feature in human type 2 diabetic subjects but because of its insolubility and low tissue concentrations, the structure of its monomer has not been determined. We describe a peptide, of calculated molecular mass 3905 Da, that was a major protein component of amyloid-rich pancreatic extracts of three type 2 diabetic patients. After collagenase treatment, an extract containing 20-50% amyloid was solubilized by sonication into 70% formic acid and the peptide was purified by gel filtration followed by reverse-phase high-performance liquid chromatography. We term this peptide diabetes-associated peptide, as it was not detected in extracts of pancreas from any of six normal subjects. Diabetes-associated peptide contains 37 amino acids and is 46% identical to the sequences of rat and human calcitonin gene-related peptide, indicating that these peptides are related in evolution. Sequence identities with conserved residues of the insulin A chain were also seen in a 16-residue segment. On extraction, the islet amyloid is particulate and insoluble like the core particles of Alzheimer disease. Their monomers have similar molecular masses, each having a hydropathic region that can probably form beta-pleated sheets. The accumulation of amyloid, including diabetes-associated peptide, in islets may impair islet function in type 2 diabetes mellitus.
Cooper
G J
GJ
Department of Biochemistry, University of Oxford, United Kingdom.
Willis
A C
AC
Clark
A
A
Turner
R C
RC
Sim
R B
RB
Reid
K B
KB
D000368:Aged; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000682:Amyloid / Q000302:isolation & purification* / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D006801:Humans; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000032:analysis / Q000378:metabolism*; D008969:Molecular Sequence Data; D009479:Neuropeptides
D000596:Amino Acids; D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D009479:Neuropeptides; D015740:Calcitonin Gene-Related Peptide