Rifampicin Does Not Prevent Amyloid Fibril Formation by Human Islet Amyloid Polypeptide but Does Inhibit Fibril Thioflavin-T Interactions: Implications for Mechanistic Studies of β-Cell Death†

Biochemistry ◽  
2008 ◽  
Vol 47 (22) ◽  
pp. 6016-6024 ◽  
Author(s):  
Fanling Meng ◽  
Peter Marek ◽  
Kathryn J. Potter ◽  
C. Bruce Verchere ◽  
Daniel P. Raleigh
Keyword(s):  
Cell Death ◽  
Amyloid Fibril ◽  
Islet Amyloid Polypeptide ◽  
Fibril Formation ◽  
Human Islet ◽  
Thioflavin T ◽  
Mechanistic Studies ◽  
Β Cell ◽  
Islet Amyloid ◽  
Amyloid Fibril Formation

scholarly journals The flanking peptides issue from the maturation of the human islet amyloid polypeptide (hIAPP) slightly modulate hIAPP-fibril formation but not hIAPP-induced cell death

Biochimie ◽  
2020 ◽  
Vol 170 ◽  
pp. 26-35 ◽  
Author(s):  
Shadai Salazar Vazquez ◽  
Bertrand Blondeau ◽  
Pierre Cattan ◽  
Mathieu Armanet ◽  
Ghislaine Guillemain ◽  
...  
Keyword(s):  
Cell Death ◽  
Islet Amyloid Polypeptide ◽  
Fibril Formation ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

scholarly journals Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation.

1990 ◽  
Vol 87 (13) ◽  
pp. 5036-5040 ◽  
Author(s):  
P. Westermark ◽  
U. Engstrom ◽  
K. H. Johnson ◽  
G. T. Westermark ◽  
C. Betsholtz
Keyword(s):  
Amino Acid ◽  
Amyloid Fibril ◽  
Islet Amyloid Polypeptide ◽  
Fibril Formation ◽  
Amino Acid Residues ◽  
Islet Amyloid ◽  
Amyloid Fibril Formation

scholarly journals Does deamidation of islet amyloid polypeptide accelerate amyloid fibril formation?

2018 ◽  
Vol 54 (98) ◽  
pp. 13853-13856 ◽  
Author(s):  
Yuko P. Y. Lam ◽  
Christopher A. Wootton ◽  
Ian Hands-Portman ◽  
Juan Wei ◽  
Cookson K. C. Chiu ◽  
...  
Keyword(s):  
Amyloid Fibril ◽  
Islet Amyloid Polypeptide ◽  
Fibril Formation ◽  
Wild Type ◽  
Islet Amyloid ◽  
Amyloid Fibril Formation

Deamidation sites of hIAPP were determined and the amount of fibril formed in mutant hIAPPs was higher than in wild-type hIAPP.

Amyloid fibril formation by partially unfolded islet amyloid polypeptide (IAPP)

2006 ◽  
pp. 721-723
Author(s):  
Aphrodite Kapurniotu ◽  
Jürgen Bernhagen ◽  
Rakez Kayed ◽  
Norma Greenfield ◽  
Herwig Brunner ◽  
...  
Keyword(s):  
Amyloid Fibril ◽  
Islet Amyloid Polypeptide ◽  
Fibril Formation ◽  
Islet Amyloid ◽  
Amyloid Fibril Formation ◽  
Partially Unfolded

Inhibition of human IAPP fibril formation does not prevent β-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP

2006 ◽  
Vol 291 (6) ◽  
pp. E1317-E1324 ◽  
Author(s):  
Juris J. Meier ◽  
Rakez Kayed ◽  
Chia-Yu Lin ◽  
Tatyana Gurlo ◽  
Leena Haataja ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Screening Tools ◽  
Β Cells ◽  
Β Cell ◽  
Islet Amyloid ◽  
Oligomer Formation ◽  
Amyloid Fibril Formation ◽  
Toxic Oligomer

Type 2 diabetes mellitus (T2DM) is characterized by an ∼60% deficit in β-cell mass, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). Human IAPP (hIAPP) forms oligomers, leading to either amyloid fibrils or toxic oligomers in an aqueous solution in vitro. Either application of hIAPP on or overexpression of hIAPP in cells induces apoptosis. It remains controversial whether the fibrils or smaller toxic oligomers induce β-cell apoptosis. Rifampicin prevents hIAPP amyloid fibril formation and has been proposed as a potential target for prevention of T2DM. We examined the actions of rifampicin on hIAPP amyloid fibril and toxic oligomer formation as well as its ability to protect β-cells from either application of hIAPP or endogenous overexpression of hIAPP (transgenic rats and adenovirus-transduced β-cells). We report that rifampicin (Acocella G. Clin Pharmacokinet 3: 108–127, 1978) prevents hIAPP fibril formation, but not formation of toxic hIAPP oligomers (Bates G. Lancet 361: 1642–1644, 2003), and does not protect β-cells from apoptosis induced by either overexpression or application of hIAPP. These data emphasize that toxic hIAPP oligomers, rather than hIAPP fibrils, initiate β-cell apoptosis and that screening tools to identify inhibitors of amyloid fibril formation are likely to be less useful than those that identify inhibitors of toxic oligomer formation. Finally, rifampicin and related molecules do not appear to be useful as candidates for prevention of T2DM.

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