scholarly journals Mechanistic Contributions of Biological Cofactors in Islet Amyloid Polypeptide Amyloidogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Phuong Trang Nguyen ◽  
Nagore Andraka ◽  
Carole Anne De Carufel ◽  
Steve Bourgault
Keyword(s):  
Type Ii Diabetes ◽  
Amyloid Fibrils ◽  
Driving Forces ◽  
Islet Amyloid Polypeptide ◽  
Type Ii Diabetes Mellitus ◽  
Major Protein ◽  
Local Concentration ◽  
Amyloid Formation ◽  
Type Ii ◽  
Islet Amyloid

Type II diabetes mellitus is associated with the deposition of fibrillar aggregates in pancreatic islets. The major protein component of islet amyloids is the glucomodulatory hormone islet amyloid polypeptide (IAPP). Islet amyloid fibrils are virtually always associated with several biomolecules, including apolipoprotein E, metals, glycosaminoglycans, and various lipids. IAPP amyloidogenesis has been originally perceived as a self-assembly homogeneous process in which the inherent aggregation propensity of the peptide and its local concentration constitute the major driving forces to fibrillization. However, over the last two decades, numerous studies have shown a prominent role of amyloid cofactors in IAPP fibrillogenesis associated with the etiology of type II diabetes. It is increasingly evident that the biochemical microenvironment in which IAPP amyloid formation occurs and the interactions of the polypeptide with various biomolecules not only modulate the rate and extent of aggregation, but could also remodel the amyloidogenesis process as well as the structure, toxicity, and stability of the resulting fibrils.

Amyloid protein in somatostatinoma differs from human islet amyloid polypeptide

1991 ◽  
Vol 124 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Haruhiko Ohsawa ◽  
Azuma Kanatsuka ◽  
Yoshiharu Tokuyama ◽  
Takahide Yamaguchi ◽  
Hideichi Makino ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type Ii Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Type Ii Diabetes Mellitus ◽  
Pancreatic Tissue ◽  
Type Ii ◽  
Pancreatic Hormones ◽  
Islet Amyloid ◽  
Electron Microscopic ◽  
Amyloid Deposits

Abstract. Amyloid deposits in somatostatinomas are rare observations. To examine the characteristics of this amyloid, we compared amyloid deposits in a somatostatinoma to those found in pancreatic tissue in patients with Type II diabetes mellitus and in insulinomas, using immunohistochemical techniques and specific antibodies to islet amyloid polypeptide or other pancreatic hormones, as well as electron-microscopy. Antibodies to islet amyloid polypeptide regions 8-17 or 25-37 were confirmed to be specific. Amyloid deposits in patients with Type II diabetes mellitus and in insulinomas, but not those in the somatostatinoma strongly reacted with these antibodies, or to an antibody to amyloid P component. Amyloid deposits in the somatostatinoma were not reactive with antibodies to somatostatin or to other pancreatic hormones. Electron-microscopic examinations revealed that amyloid fibrils in the somatostatinoma were thinner and more randomly distributed than were those in islets from patients with Type II diabetes mellitus. As amyloid in somatostatinomas is unlike that consisting of islet amyloid polypeptide or other mature pancreatic hormones, it may be a novel type of local amyloid in pancreatic islets.

scholarly journals Brazilin inhibits fibrillogenesis of human islet amyloid polypeptide, disassembles mature fibrils, and alleviates cytotoxicity

RSC Advances ◽  
2017 ◽  
Vol 7 (69) ◽  
pp. 43491-43501 ◽  
Author(s):  
Jingjing Guo ◽  
Wanqi Sun ◽  
Li Li ◽  
Fufeng Liu ◽  
Wenyu Lu
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Simulation ◽  
Type Ii Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Type Ii Diabetes Mellitus ◽  
Inhibitory Effect ◽  
Human Islet ◽  
Type Ii ◽  
Islet Amyloid ◽  
Simulation Experiments

Inhibitory effect of brazilin on the fibrillogenesis of hIAPP was explored using biochemical, biophysical, cytobiological and molecular simulation experiments. Brazilin was a potential compound for therapeutic treatment of type II diabetes mellitus.

scholarly journals Extensive islet amyloid formation is induced by development of Type II diabetes mellitus and contributes to its progression: pathogenesis of diabetes in a mouse model

Diabetologia ◽  
1999 ◽  
Vol 42 (4) ◽  
pp. 427-434 ◽  
Author(s):  
J. W. M. Höppener ◽  
C. Oosterwijk ◽  
M. G. Nieuwenhuis ◽  
G. Posthuma ◽  
J. H. H. Thijssen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Mouse Model ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Amyloid Formation ◽  
Type Ii ◽  
Islet Amyloid

scholarly journals Influence of a curcumin derivative on hIAPP aggregation in the absence and presence of lipid membranes

2016 ◽  
Vol 52 (5) ◽  
pp. 942-945 ◽  
Author(s):  
Amit S. Pithadia ◽  
Anirban Bhunia ◽  
Rajendran Sribalan ◽  
Vediappen Padmini ◽  
Carol A. Fierke ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Lipid Membranes ◽  
Type Ii Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Type Ii Diabetes Mellitus ◽  
Human Islet ◽  
Type Ii ◽  
Β Cells ◽  
Islet Amyloid ◽  
Curcumin Derivative

The deposition of aggregates of human islet amyloid polypeptide (hIAPP) has been correlated with the death of β-cells in type II diabetes mellitus.

scholarly journals γ-AApeptides–based Small Molecule Ligands That Disaggregate Human Islet Amyloid Polypeptide

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Olapeju Bolarinwa ◽  
Chunpu Li ◽  
Nawal Khadka ◽  
Qi Li ◽  
Yan Wang ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Typical Feature ◽  
Human Islet ◽  
Type Ii ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Age Related ◽  
Small Molecule Ligands ◽  
Human Amylin

AbstractThe abnormal folding and aggregation of functional proteins into amyloid is a typical feature of many age-related diseases, including Type II diabetes. Growing evidence has revealed that the prevention of aggregate formation in culprit proteins could retard the progression of amyloid diseases. Human Amylin, also known as human islet amyloid polypeptide (hIAPP), is the major factor for categorizing Type II diabetes as an amyloid disease. Specifically, hIAPP has a great aggregation potential, which always results in a lethal situation for the pancreas. Many peptide inhibitors have been constructed from the various segments of the full-length hIAPP peptide; however, only a few have their origin from the screening of combinatorial peptidomimetic library. In this study, based on HW-155, which was previously discovered from a one–bead–one compound (OBOC) library to inhibit Aβ40 aggregation, we investigated eight (8) analogues and evaluated their amyloid-prevention capabilities for inhibiting fibrillization of hIAPP. Characterization studies revealed that all analogues of HW-155, as well as HW-155, were effective inhibitors of the fibril formation by hIAPP.

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.

Sign in / Sign up

Export Citation Format

Share Document