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

Abstract

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 β 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.

• Authors: Diana Ribeiro, Istvan Horvath, Nikki Heath, Ryan Hicks, Anna Forslöw, Pernilla Wittung-Stafshede
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 114 Issue 42 Pg. 11127-11132 (10 17 2017) ISSN: 1091-6490 [Electronic] United States
• PMID: 28973954 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Islet Amyloid Polypeptide

Topics

• Adult
• Aged
• Case-Control Studies
• Diabetes Mellitus, Type 2 (metabolism)
• Extracellular Vesicles (physiology)
• Female
• Humans
• Islet Amyloid Polypeptide (metabolism)
• Islets of Langerhans (metabolism)
• Male
• Middle Aged
• Plaque, Amyloid (metabolism)
• Young Adult