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.

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

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.

Genetic background determines the extent of islet amyloid formation in human islet amyloid polypeptide transgenic mice

2005 ◽  
Vol 289 (4) ◽  
pp. E703-E709 ◽  
Author(s):  
Rebecca L. Hull ◽  
Melissah R. Watts ◽  
Keiichi Kodama ◽  
Zhen-ping Shen ◽  
Kristina M. Utzschneider ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Genetic Background ◽  
Cell Mass ◽  
Islet Amyloid Polypeptide ◽  
Amyloid Deposition ◽  
Human Islet ◽  
Amyloid Formation ◽  
Β Cell ◽  
Islet Amyloid ◽  
Background Strain

Genetic background is important in determining susceptibility to metabolic abnormalities such as insulin resistance and β-cell dysfunction. Islet amyloid is associated with reduced β-cell mass and function and develops in the majority of our C57BL/6J × DBA/2J (F1) male human islet amyloid polypeptide (hIAPP) transgenic mice after 1 yr of increased fat feeding. To determine the relative contribution of each parental strain, C57BL/6J (BL6) and DBA/2J (DBA2), to islet amyloid formation, we studied male hIAPP mice on each background strain (BL6, n = 13; and DBA2 n = 11) and C57BL/6J × DBA/2J F1mice ( n = 17) on a 9% (wt/wt) fat diet for 1 yr. At the end of 12 mo, islet amyloid deposition was quantified from thioflavin S-stained pancreas sections. The majority of mice in all groups developed islet amyloid (BL6: 91%, F1: 76%, DBA2: 100%). However, the prevalence (%amyloid-positive islets; BL6: 14 ± 3%, F1: 44 ± 8%, DBA2: 49 ± 9%, P < 0.05) and severity (%islet area occupied by amyloid; BL6: 0.03 ± 0.01%, F1: 9.2 ± 2.9%, DBA2: 5.7 ± 2.3%, p ≤ 0.01) were significantly lower in BL6 than F1and DBA2 mice. Increased islet amyloid severity was negatively correlated with insulin-positive area per islet, in F1( r2= 0.75, P < 0.001) and DBA2 ( r2= 0.87, P < 0.001) mice but not BL6 mice ( r2= 0.07). In summary, the extent of islet amyloid formation in hIAPP transgenic mice is determined by background strain, with mice expressing DBA/2J genes (F1and DBA2 mice) being more susceptible to amyloid deposition that replaces β-cell mass. These findings underscore the importance of genetic and environmental factors in studying metabolic disease.

Human islet amyloid polypeptide accumulates at similar sites in islets of transgenic mice and humans

Diabetes ◽  
1994 ◽  
Vol 43 (5) ◽  
pp. 640-644 ◽  
Author(s):  
E. J. de Koning ◽  
J. W. Hoppener ◽  
J. S. Verbeek ◽  
C. Oosterwijk ◽  
K. L. van Hulst ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

Oligotyrosines Inhibit Amyloid Formation of Human Islet Amyloid Polypeptide in a Tyrosine-Number-Dependent Manner

2018 ◽  
Vol 5 (2) ◽  
pp. 1092-1099 ◽  
Author(s):  
Yanru Xin ◽  
Huazhi Zhang ◽  
Qigang Hu ◽  
Sidan Tian ◽  
Chenhui Wang ◽  
...  
Keyword(s):  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Amyloid Formation ◽  
Dependent Manner ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

scholarly journals Graphene quantum dots against human IAPP aggregation and toxicity in vivo

Nanoscale ◽  
2018 ◽  
Vol 10 (42) ◽  
pp. 19995-20006 ◽  
Author(s):  
Miaoyi Wang ◽  
Yunxiang Sun ◽  
Xueying Cao ◽  
Guotao Peng ◽  
Ibrahim Javed ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Islet Amyloid Polypeptide ◽  
Graphene Quantum Dots ◽  
Human Islet ◽  
Zebrafish Embryos ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

Graphene quantum dots are biocompatible zero-dimensional nanostructures, which displayed a potency in rescuing zebrafish embryos from the toxicity of human islet amyloid polypeptide.

scholarly journals Loss of perlecan heparan sulfate glycosaminoglycans lowers body weight and decreases islet amyloid deposition in human islet amyloid polypeptide transgenic mice

2019 ◽  
Vol 32 (2) ◽  
pp. 95-102
Author(s):  
Andrew T Templin ◽  
Mahnaz Mellati ◽  
Raija Soininen ◽  
Meghan F Hogan ◽  
Nathalie Esser ◽  
...  
Keyword(s):  
Body Weight ◽  
Transgenic Mice ◽  
Heparan Sulfate ◽  
Islet Amyloid Polypeptide ◽  
Amyloid Deposition ◽  
Secretory Product ◽  
Cell Area ◽  
Β Cell ◽  
Islet Amyloid

Abstract Islet amyloid is a pathologic feature of type 2 diabetes (T2D) that is associated with β-cell loss and dysfunction. These amyloid deposits form via aggregation of the β-cell secretory product islet amyloid polypeptide (IAPP) and contain other molecules including the heparan sulfate proteoglycan perlecan. Perlecan has been shown to bind amyloidogenic human IAPP (hIAPP) via its heparan sulfate glycosaminoglycan (HS GAG) chains and to enhance hIAPP aggregation in vitro. We postulated that reducing the HS GAG content of perlecan would also decrease islet amyloid deposition in vivo. hIAPP transgenic mice were crossed with Hspg2Δ3/Δ3 mice harboring a perlecan mutation that prevents HS GAG attachment (hIAPP;Hspg2Δ3/Δ3), and male offspring from this cross were fed a high fat diet for 12 months to induce islet amyloid deposition. At the end of the study body weight, islet amyloid area, β-cell area, glucose tolerance and insulin secretion were analyzed. hIAPP;Hspg2Δ3/Δ3 mice exhibited significantly less islet amyloid deposition and greater β-cell area compared to hIAPP mice expressing wild type perlecan. hIAPP;Hspg2Δ3/Δ3 mice also gained significantly less weight than other genotypes. When adjusted for differences in body weight using multiple linear regression modeling, we found no differences in islet amyloid deposition or β-cell area between hIAPP transgenic and hIAPP;Hspg2Δ3/Δ3 mice. We conclude that loss of perlecan exon 3 reduces islet amyloid deposition in vivo through indirect effects on body weight and possibly also through direct effects on hIAPP aggregation. Both of these mechanisms may promote maintenance of glucose homeostasis in the setting of T2D.

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