Proteoglycans synthesized and secreted by pancreatic islet beta-cells bind amylin.
Pancreatic islet amyloid deposits in type 2 diabetes are associated with decreased islet beta-cell function. They contain both amylin (islet amyloid polypeptide), the beta-cell-derived unique fibrillogenic component, and heparan sulfate proteoglycans (HSPGs). We hypothesized that beta-cell HSPGs contribute to islet amyloidogenesis. [35S]Sulfate-labeled proteoglycans from islet-derived beta-TC3 cell cultures eluted from diethylaminoethyl Sephacel at 0.35M NaCl. Chromatography on Sepharose CL-4B and SDS-PAGE analysis revealed distinct populations of proteoglycans. Medium HSPGs eluted at K(av) approximately 0.18 and 0.50 with glycosaminoglycan chains of approximately 28 and 19 kDa, respectively. A third population containing chondroitin/dermatan sulfate eluted at K(av) approximately 0.70 with glycosaminoglycan chains of approximately 10 kDa. A single size class of heparan and chondroitin/dermatan sulfate proteoglycans in the cell layer eluted at K(av) approximately 0.40 with glycosaminoglycan chains of approximately 19 kDa. Medium and cell layer proteoglycans bound exclusively to fibrillogenic amylin, as determined by gel mobility shift assays, indicating a possible role for beta-cell-derived proteoglycans in islet amyloid formation.
The Hope Heart Institute, Seattle, WA 98104, USA.
Susan
S
Potter-Perigo
Rebecca L
RL
Hull
Christina
C
Tsoi
Kathleen R
KR
Braun
Sofianos
S
Andrikopoulos
Jeanette
J
Teague
C
C
Bruce Verchere
Steven E
SE
Kahn
Thomas N
TN
Wight
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002845:Chromatography; D002852:Chromatography, Ion Exchange; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006025:Glycosaminoglycans / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D011485:Protein Binding
D000682:Amyloid; D006025:Glycosaminoglycans; D019812:Heparan Sulfate Proteoglycans; D058228:Islet Amyloid Polypeptide