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

2017 ◽  
Vol 114 (42) ◽  
pp. 11127-11132 ◽  
Author(s):  
Diana Ribeiro ◽  
Istvan Horvath ◽  
Nikki Heath ◽  
Ryan Hicks ◽  
Anna Forslöw ◽  
...  
Keyword(s):  
Pancreatic Islets ◽  
Extracellular Vesicles ◽  
Islet Amyloid Polypeptide ◽  
Cell Communication ◽  
Human Islet ◽  
Amyloid Formation ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Amyloid Deposits

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.

scholarly journals Amyloid Formation in Response to β Cell Stress Occurs In Vitro, but Not In Vivo, in Islets of Transgenic Mice Expressing Human Islet Amyloid Polypeptide

1995 ◽  
Vol 1 (5) ◽  
pp. 542-553 ◽  
Author(s):  
Gunilla Westermark ◽  
Michelle Benig Arora ◽  
Niles Fox ◽  
Raymond Carroll ◽  
Shu Jin Chan ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Cell Stress ◽  
Amyloid Formation ◽  
Β Cell ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

scholarly journals Human Islet Amyloid Polypeptide Fibril Binding to Catalase: A Transmission Electron Microscopy and Microplate Study

2010 ◽  
Vol 10 ◽  
pp. 879-893 ◽  
Author(s):  
Nathaniel G. N. Milton ◽  
J. Robin Harris
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Islet Amyloid Polypeptide ◽  
Amyloid Β ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Transmission Electron

The diabetes-associated human islet amyloid polypeptide (IAPP) is a 37-amino-acid peptide that forms fibrilsin vitroandin vivo. Human IAPP fibrils are toxic in a similar manner to Alzheimer's amyloid-β (Aβ) and prion protein (PrP) fibrils. Previous studies have shown that catalase binds to Aβ fibrils and appears to recognize a region containing the Gly-Ala-Ile-Ile sequence that is similar to the Gly-Ala-Ile-Leu sequence found in human IAPP residues 24-27. This study presents a transmission electron microscopy (TEM)—based analysis of fibril formation and the binding of human erythrocyte catalase to IAPP fibrils. The results show that human IAPP 1-37, 8-37, and 20-29 peptides form fibrils with diverse and polymorphic structures. All three forms of IAPP bound catalase, and complexes of IAPP 1-37 or 8-37 with catalase were identified by immunoassay. The binding of biotinylated IAPP to catalase was high affinity with a KDof 0.77nM, and could be inhibited by either human or rat IAPP 1-37 and 8-37 forms. Fibrils formed by the PrP 118-135 peptide with a Gly-Ala-Val-Val sequence also bound catalase. These results suggest that catalase recognizes a Gly-Ala-Ile-Leu—like sequence in amyloid fibril-forming peptides. For IAPP 1-37 and 8-37, the catalase binding was primarily directed towards fibrillar rather than ribbon-like structures, suggesting differences in the accessibility of the human IAPP 24-27 Gly-Ala-Ile-Leu region. This suggests that catalase may be able to discriminate between different structural forms of IAPP fibrils. The ability of catalase to bind IAPP, Aβ, and PrP fibrils demonstrates the presence of similar accessible structural motifs that may be targets for antiamyloid therapeutic development.

Extended life span is associated with insulin resistance in a transgenic mouse model of insulinoma secreting human islet amyloid polypeptide

2004 ◽  
Vol 286 (3) ◽  
pp. E418-E424 ◽  
Author(s):  
Sofianos Andrikopoulos ◽  
Rebecca L. Hull ◽  
C. Bruce Verchere ◽  
Feng Wang ◽  
Shani M. Wilbur ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Life Span ◽  
Amyloid Fibrils ◽  
Islet Amyloid Polypeptide ◽  
Transgenic Animals ◽  
Human Islet ◽  
Amyloid Formation ◽  
Islet Amyloid ◽  
Glucose Levels ◽  
Human Islet Amyloid Polypeptide

Pancreatic amyloid is found in patients with insulinomas and type 2 diabetes. To study mechanisms of islet amyloidogenesis, we produced transgenic mice expressing the unique component of human islet amyloid, human islet amyloid polypeptide (hIAPP). These mice develop islet amyloid after 12 mo of high-fat feeding. To determine whether we could accelerate the rate of islet amyloid formation, we crossbred our hIAPP transgenic animals with RIP-Tag mice that develop islet tumors and die at 12 wk of age from hypoglycemia. At 12 wk of age, this new line of hIAPP×RIP-Tag mice was heavier (29.7 ± 1.0 vs. 25.0 ± 1.3 g, P < 0.05) and had increased plasma glucose levels (4.6 ± 0.4 vs. 2.9 ± 0.6 mmol/l, P < 0.05) compared with littermate RIP-Tag mice. However, the hIAPP×RIP-Tag mice did not display islet amyloid or amyloid fibrils despite high circulating hIAPP levels (24.6 ± 7.0 pmol/l). Interestingly, hIAPP×RIP-Tag mice had a longer life span than RIP-Tag mice (121 ± 8 vs. 102 ± 5 days, P < 0.05). This increase in life span in hIAPP×RIP-Tag was positively correlated with body weight ( r = 0.48, P < 0.05) and was associated with decreased insulin sensitivity compared with RIP-Tag mice. hIAPP×RIP-Tag mice did not develop amyloid during their 4-mo life span, suggesting that increased hIAPP secretion is insufficient for islet amyloid formation within such a short time. However, hIAPP×RIP-Tag mice did have an increase in life span that was associated with insulin resistance, suggesting that hIAPP has extrapancreatic effects, possibly on peripheral glucose metabolism.

Bisphenol analogues differently affect human islet polypeptide amyloid formation

RSC Advances ◽  
2016 ◽  
Vol 6 (9) ◽  
pp. 7239-7248 ◽  
Author(s):  
Lizi Huang ◽  
Mingyan Liao ◽  
Xin Yang ◽  
Hao Gong ◽  
Liang Ma ◽  
...  
Keyword(s):  
Plastic Material ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Causal Factor ◽  
Amyloid Formation ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Bisphenol Analogues

Bisphenols (BPs) are widely used in the production of plastic material, misfolded human islet amyloid polypeptide (hIAPP) is a causal factor in diabetes. We demonstrated BPs analogues show different effects on hIAPP amyloid formation.

Oophorectomy promotes islet amyloid formation in human islet amyloid polypeptide transgenic mice

Diabetes ◽  
2001 ◽  
Vol 50 (Supplement 1) ◽  
pp. S184-S185 ◽  
Author(s):  
R. L. Hull ◽  
B. Verchere ◽  
S. Andrikopoulos ◽  
F. Wang ◽  
J. Vidal ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Amyloid Formation ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide
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