title: Measurement of Pro-Islet Amyloid Polypeptide (1-48) in Diabetes and Islet Transplants.
abstract: Islet amyloid is a feature of β-cell failure in type 2 diabetes (T2D) and type 1 diabetes (T1D) recipients of islet transplants. Islet amyloid contains islet amyloid polypeptide (IAPP; amylin), a circulating peptide that is produced in β cells by processing of its precursor, proIAPP1-67, via an intermediate form, proIAPP1-48. Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in β-cell prohormone processing.
  
  
  
  Determine whether plasma levels of precursor forms of IAPP are elevated in diabetes.
  
  
  
  We developed an immunoassay to detect proIAPP1-48 in human plasma, and we determined the ratio of proIAPP1-48 to mature IAPP in subjects with T1D, T2D, recipients of islet transplants, and healthy controls.
  
  
  
  The proIAPP1-48 immunoassay had a limit of detection of 0.18 ± 0.06 pM and cross-reactivity with intact proIAPP1-67 <15%. Healthy individuals had plasma concentrations of proIAPP1-48 immunoreactivity of 1.5 ± 0.2 pM and a proIAPP1-48 to total IAPP ratio of 0.28 ± 0.03. Plasma concentrations of proIAPP1-48 immunoreactivity were not significantly different in subjects with T2D but were markedly increased in T1D recipients of islet transplants. Children and adults with T1D had reduced mature IAPP levels relative to age-matched controls but an elevated ratio of proIAPP1-48 to total IAPP.
  
  
  
  The β cells in T1D and islet transplants have impaired processing of the proIAPP1-48 intermediate. The ratio of proIAPP1-48-to-IAPP immunoreactivity may have value as a biomarker of β-cell stress and dysfunction.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.|Research Institute, BC Children's Hospital, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Jaques A
authors.initials: JA
authors.lastname: Courtade
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.|Research Institute, BC Children's Hospital, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Agnieszka M
authors.initials: AM
authors.lastname: Klimek-Abercrombie
authors.affiliation: Research Institute, BC Children's Hospital, Vancouver, British Columbia V5Z 4H4, Canada.|Department of Surgery, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chen
authors.affiliation: American Laboratory Products Company, Salem, New Hampshire 03079.
authors.forename: Nirja
authors.initials: N
authors.lastname: Patel
authors.affiliation: Research Institute, BC Children's Hospital, Vancouver, British Columbia V5Z 4H4, Canada.|Department of Genetics, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Phoebe Y T
authors.initials: PYT
authors.lastname: Lu
authors.affiliation: Diabetes Clinical Research Program, Benaroya Research Institute, Seattle, Washington 98101.
authors.forename: Cate
authors.initials: C
authors.lastname: Speake
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.|Research Institute, BC Children's Hospital, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Orban
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington 98195.
authors.forename: Behzad
authors.initials: B
authors.lastname: Najafian
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Graydon
authors.initials: G
authors.lastname: Meneilly
authors.affiliation: Diabetes Clinical Research Program, Benaroya Research Institute, Seattle, Washington 98101.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.affiliation: Department of Surgery, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Garth L
authors.initials: GL
authors.lastname: Warnock
authors.affiliation: Research Institute, BC Children's Hospital, Vancouver, British Columbia V5Z 4H4, Canada.|Department of Medicine, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: Constadina
authors.initials: C
authors.lastname: Panagiotopoulos
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.|Research Institute, BC Children's Hospital, Vancouver, British Columbia V5Z 4H4, Canada.|Department of Surgery, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada.
authors.forename: C Bruce
authors.initials: CB
authors.lastname: Verchere
mesh_terms: D000328:Adult; D000682:Amyloid / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay; D058228:Islet Amyloid Polypeptide / Q000097:blood*; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000378:metabolism; D012016:Reference Values; D018570:Risk Assessment
chemical_list: D000682:Amyloid; D015415:Biomarkers; D058228:Islet Amyloid Polypeptide; C422904:pro-islet amyloid polypeptide; D011384:Proinsulin