PMID- 22847497
OWN - NLM
STAT- MEDLINE
DCOM- 20130308
LR  - 20211021
IS  - 1938-2022 (Electronic)
IS  - 1938-2014 (Print)
IS  - 1938-2014 (Linking)
VI  - 4
IP  - 3
DP  - 2012 May-Jun
TI  - Islet amyloid polypeptide in pancreatic islets from type 2 diabetic subjects.
PG  - 223-32
LID - 10.4161/isl.20477 [doi]
AB  - AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP) is a chief constituent of 
      amyloid deposits in pancreatic islets, characteristic histopathology for type 2 
      diabetes. The goal of this study was to analyze islet cell composition in 
      diabetic islets for the process of transforming water-soluble IAPP in beta-cells to 
      water-insoluble amyloid deposits by Immunocytochemical staining using different 
      dilutions of anti-IAPP antibody. IAPP in beta-cell granules may initiate beta-cell 
      necrosis through apoptosis to form interstitial amyloid deposits in type 2 
      diabetic islets. RESULTS: Control islets revealed twice as much beta-cells as 
      alpha-cells whereas 15 of 18 type 2 diabetic cases (83%) revealed alpha- cells as major 
      cells in larger islets. Diabetic islets consisted of more larger islets with more 
      sigma-cells than beta-cells, which contribute to hyperglucagonemia. In control islets, 
      percentage of IAPP-positive cells against beta-cells was 40-50% whereas percentage 
      for type 2 diabetic islets was about 25%. Amyloid deposits in diabetic islets 
      were not readily immunostained for IAPP using 1: 800 diluted antibody, however, 
      1: 400 and 1: 200 diluted solutions provided stronger immunostaining in early 
      stages of islet amyloidogenesis after treating the deparaffinized sections with 
      formic acid. METHODS: Using commercially available rabbit antihuman IAPP 
      antibody, immunocytochemical staining was performed on 18 cases of pancreatic 
      tissues from type 2 diabetic subjects by systematically immunostaining for 
      insulin, glucagon, somatostatin (SRIF) and IAPP compared with controls. Sizes of 
      islets were measured by 1 cm scale, mounted in 10X eye piece. 
      CONCLUSIONS/INTERPRETATION: alpha cells were major islet cells in majority of 
      diabetic pancreas (83%) and all diabetic islets contained less IAPP-positive 
      cells than controls, indicating that IAPP deficiency in pancreatic islets is 
      responsible for decreased IAPP in blood. In diabetic islets, water-soluble IAPP 
      disappeared in beta-cell granules, which transformed to water-insoluble amyloid 
      deposits. Amyloid deposits were not readily immunostained using IAPP 1: 800 
      diluted antibody but were stronger immunostained for IAPP in early stages of 
      amyloid deposited islets using less diluted solutions after formic acid 
      treatment. In early islet amyloidogenesis, dying beta-cell cytoplasm was adjacently 
      located to fine amyloid fibrils, supporting that IAPP in secretary granules from 
      dying beta cells served as nidus for islet beta-sheet formation.
FAU - Tomita, Tatsuo
AU  - Tomita T
AD  - Department of Integrative Bioscience, Oregon National Primate Center, Oregon 
      Health and Science University, Portland, OR, USA. tomitat@ohsu.edu
LA  - eng
GR  - RR 00063/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Islets
JT  - Islets
JID - 101495366
RN  - 0 (Insulin)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 51110-01-1 (Somatostatin)
RN  - 9007-92-5 (Glucagon)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Diabetes Mellitus, Type 2/*metabolism/pathology
MH  - Female
MH  - Glucagon/metabolism
MH  - Glucagon-Secreting Cells/*metabolism/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - Insulin/metabolism
MH  - Insulin-Secreting Cells/*metabolism/pathology
MH  - Islet Amyloid Polypeptide/*metabolism
MH  - Islets of Langerhans/cytology/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Somatostatin/metabolism
PMC - PMC3442820
EDAT- 2012/08/01 06:00
MHDA- 2013/03/09 06:00
PMCR- 2013/05/01
CRDT- 2012/08/01 06:00
PHST- 2012/08/01 06:00 [entrez]
PHST- 2012/08/01 06:00 [pubmed]
PHST- 2013/03/09 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - 20477 [pii]
AID - 2012ISLETS0006R [pii]
AID - 10.4161/isl.20477 [doi]
PST - ppublish
SO  - Islets. 2012 May-Jun;4(3):223-32. doi: 10.4161/isl.20477.