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 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.

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 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.

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.

scholarly journals Influence of Aluminium and EGCG on Fibrillation and Aggregation of Human Islet Amyloid Polypeptide

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Zhi-Xue Xu ◽  
Qiang Zhang ◽  
Gong-Li Ma ◽  
Cong-Heng Chen ◽  
Yan-Ming He ◽  
...  
Keyword(s):  
Type Ii Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Epigallocatechin Gallate ◽  
Inhibitory Effect ◽  
Human Islet ◽  
Molar Ratio ◽  
Type Ii ◽  
Amyloid Proteins ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

The abnormal fibrillation of human islet amyloid polypeptide (hIAPP) has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (−)-epigallocatechin gallate (EGCG) is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III)/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III) and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III) and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III) could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III)/EGCG complex in molar ratio of 1 : 1 as Al(EGCG)(H2O)2 could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes.

Human islet amyloid polypeptide (hIAPP) - a curse in type II diabetes mellitus: insights from structure and toxicity studies

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Ajit Kumar Bishoyi ◽  
Pratiksha H. Roham ◽  
Kavitha Rachineni ◽  
Shreyada Save ◽  
M. Asrafuddoza Hazari ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Islet Amyloid Polypeptide ◽  
Peptide Hormone ◽  
Type Ii Diabetes Mellitus ◽  
Human Islet ◽  
Random Structure ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Toxicity Studies

AbstractThe human islet amyloid polypeptide (hIAPP) or amylin, a neuroendocrine peptide hormone, is known to misfold and form amyloidogenic aggregates that have been observed in the pancreas of 90% subjects with Type 2 Diabetes Mellitus (T2DM). Under normal physiological conditions, hIAPP is co-stored and co-secreted with insulin; however, under chronic hyperglycemic conditions associated with T2DM, the overexpression of hIAPP occurs that has been associated with the formation of amyloid deposits; as well as the death and dysfunction of pancreatic β-islets in T2DM. Hitherto, various biophysical and structural studies have shown that during this process of aggregation, the peptide conformation changes from random structure to helix, then to β-sheet, subsequently to cross β-sheets, which finally form left-handed helical aggregates. The intermediates, formed during this process, have been shown to induce higher cytotoxicity in the β-cells by inducing cell membrane disruption, endoplasmic reticulum stress, mitochondrial dysfunction, oxidative stress, islet inflammation, and DNA damage. As a result, several research groups have attempted to target both hIAPP aggregation phenomenon and the destabilization of preformed fibrils as a therapeutic intervention for T2DM management. In this review, we have summarized structural aspects of various forms of hIAPP viz. monomer, oligomers, proto-filaments, and fibrils of hIAPP. Subsequently, cellular toxicity caused by toxic conformations of hIAPP has been elaborated upon. Finally, the need for performing structural and toxicity studies in vivo to fill in the gap between the structural and cellular aspects has been discussed.

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 Inhibition of IAPP Aggregation and Toxicity by Natural Products and Derivatives

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Amit Pithadia ◽  
Jeffrey R. Brender ◽  
Carol A. Fierke ◽  
Ayyalusamy Ramamoorthy
Keyword(s):  
Natural Products ◽  
Small Molecules ◽  
Type Ii Diabetes ◽  
Pancreatic Beta Cell ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Pathological Feature ◽  
Type Ii ◽  
Cell Toxicity ◽  
Islet Amyloid

Fibrillar aggregates of human islet amyloid polypeptide, hIAPP, a pathological feature seen in some diabetes patients, are a likely causative agent for pancreatic beta-cell toxicity, leading to a transition from a state of insulin resistance to type II diabetes through the loss of insulin producing beta-cells by hIAPP induced toxicity. Because of the probable link between hIAPP and the development of type II diabetes, there has been strong interest in developing reagents to study the aggregation of hIAPP and possible therapeutics to block its toxic effects. Natural products are a class of compounds with interesting pharmacological properties against amyloids which have made them interesting targets to study hIAPP. Specifically, the ability of polyphenolic natural products, EGCG, curcumin, and resveratrol, to modulate the aggregation of hIAPP is discussed. Furthermore, we have outlined possible mechanistic discoveries of the interaction of these small molecules with the peptide and how they may mitigate toxicity associated with peptide aggregation. These abundantly found agents have been long used to combat diseases for many years and may serve as useful templates toward developing therapeutics against hIAPP aggregation and toxicity.

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