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Extracellular vesicles from human pancreatic islets suppress human islet amyloid polypeptide amyloid formation

Diana Ribeiro (Institutionen för biologi och bioteknik, Kemisk biologi) ; Istvan Horvath (Institutionen för biologi och bioteknik, Kemisk biologi) ; N. Heath ; R. Hicks ; A. Forslow ; Pernilla Wittung-Stafshede (Institutionen för biologi och bioteknik, Kemisk biologi)
Proceedings of the National Academy of Sciences of the United States of America (0027-8424). Vol. 114 (2017), 42, p. 11127-11132.
[Artikel, refereegranskad vetenskaplig]

Extracellular vesicles (EVs) are small vesicles released by cells to aid cell-cell communication and tissue homeostasis. Human islet amyloid polypeptide (IAPP) is the major component of amyloid deposits found in pancreatic islets of patients with type 2 diabetes (T2D). IAPP is secreted in conjunction with insulin from pancreatic beta cells to regulate glucose metabolism. Here, using a combination of analytical and biophysical methods in vitro, we tested whether EVs isolated from pancreatic islets of healthy patients and patients with T2D modulate IAPP amyloid formation. We discovered that pancreatic EVs from healthy patients reduce IAPP amyloid formation by peptide scavenging, but T2D pancreatic and human serum EVs have no effect. In accordance with these differential effects, the insulin: C-peptide ratio and lipid composition differ between EVs from healthy pancreas and EVs from T2D pancreas and serum. It appears that healthy pancreatic EVs limit IAPP amyloid formation via direct binding as a tissue-specific control mechanism.

Nyckelord: extracellular vesicles, type 2 diabetes, amyloid, atomic force microscopy, electron microscopy

Denna post skapades 2017-11-10. Senast ändrad 2017-12-27.
CPL Pubid: 253059


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Pancreatic extracellular communication. Applications to beta cell cultures and islet amyloid polypeptide aggregation