Analysis of amylin cleavage products provides new insights into the amyloidogenic region of human amylin

1999 ◽  
Vol 294 (5) ◽  
pp. 1375-1385 ◽  
Author(s):  
Melanie R Nilsson ◽  
Daniel P Raleigh
Keyword(s):  
Amyloidogenic Region ◽  
Human Amylin

Effects of pramlintide, an analog of human amylin, on plasma glucose profiles in patients with IDDM: results of a multicenter trial

Diabetes ◽  
1997 ◽  
Vol 46 (4) ◽  
pp. 632-636 ◽  
Author(s):  
R. G. Thompson ◽  
J. Peterson ◽  
A. Gottlieb ◽  
J. Mullane
Keyword(s):  
Plasma Glucose ◽  
Multicenter Trial ◽  
Glucose Profiles ◽  
Human Amylin

scholarly journals α-CGRP disrupts amylin fibrillization and regulates insulin secretion: implications on diabetes and migraine

2021 ◽  
Vol 12 (16) ◽  
pp. 5853-5864
Author(s):  
Amber L. H. Gray ◽  
Aleksandra Antevska ◽  
Benjamin A. Link ◽  
Bryan Bogin ◽  
Susan J. Burke ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Protective Effect ◽  
Human Insulin ◽  
Human Amylin

CGRP concentration is elevated in migraine conditions. The protective effect of migraine against type 2 diabetes is attributed to the ability of CGRP to remodel human amylin aggregation and to suppress the secretion of mouse insulin 2 (the orthologue of human insulin).

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.

Inhibition of Amyloid Fibril Formation of Human Amylin by N-Alkylated Amino Acid and -Hydroxy Acid Residue Containing Peptides

2002 ◽  
Vol 8 (18) ◽  
pp. 4285-4291 ◽  
Author(s):  
Dirk T. S. Rijkers ◽  
Jo W. M. Höppener ◽  
George Posthuma ◽  
Cornelis J. M. Lips ◽  
Rob M. J. Liskamp
Keyword(s):  
Amino Acid ◽  
Hydroxy Acid ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Amyloid Fibril Formation ◽  
Human Amylin

scholarly journals Sedimentation Studies on Human Amylin Fail to Detect Low-Molecular-Weight Oligomers

2008 ◽  
Vol 94 (7) ◽  
pp. L45-L47 ◽  
Author(s):  
Sara M. Vaiana ◽  
Rodolfo Ghirlando ◽  
Wai-Ming Yau ◽  
William A. Eaton ◽  
James Hofrichter
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Human Amylin

scholarly journals Tetracycline Treatment Retards the Onset and Slows the Progression of Diabetes in Human Amylin/Islet Amyloid Polypeptide Transgenic Mice

Diabetes ◽  
2009 ◽  
Vol 59 (1) ◽  
pp. 161-171 ◽  
Author(s):  
J. F. Aitken ◽  
K. M. Loomes ◽  
D. W. Scott ◽  
S. Reddy ◽  
A. R.J. Phillips ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Islet Amyloid Polypeptide ◽  
Islet Amyloid ◽  
Tetracycline Treatment ◽  
Human Amylin

The chaperone proteins HSP70, HSP40/DnaJ and GRP78/BiP suppress misfolding and formation of β-sheet-containing aggregates by human amylin: a potential role for defective chaperone biology in Type 2 diabetes

2010 ◽  
Vol 432 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Vita Chien ◽  
Jacqueline F. Aitken ◽  
Shaoping Zhang ◽  
Christina M. Buchanan ◽  
Anthony Hickey ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Potential Role ◽  
Β Cell ◽  
Molar Ratios ◽  
Irreversible Aggregation ◽  
Chaperone Binding ◽  
Human Amylin ◽  
Β Sheet ◽  
Glucose Regulated Protein

Misfolding of the islet β-cell peptide hA (human amylin) into β-sheet-containing oligomers is linked to β-cell apoptosis and the pathogenesis of T2DM (Type 2 diabetes mellitus). In the present study, we have investigated the possible effects on hA misfolding of the chaperones HSP (heat-shock protein) 70, GRP78/BiP (glucose-regulated protein of 78 kDa/immunoglobulin heavy-chain-binding protein) and HSP40/DnaJ. We demonstrate that hA underwent spontaneous time-dependent β-sheet formation and aggregation by thioflavin-T fluorescence in solution, whereas rA (rat amylin) did not. HSP70, GRP78/BiP and HSP40/DnaJ each independently suppressed hA misfolding. Maximal molar protein/hA ratios at which chaperone activity was detected were 1:200 (HSP70, HSP40/DnaJ and GRP78/BiP). By contrast, none of the chaperones modified the secondary structure of rA. hA, but not rA, was co-precipitated independently with HSP70 and GRP78/BiP by anti-amylin antibodies. As these effects occur at molar ratios consistent with chaperone binding to relatively rare misfolded hA species, we conclude that HSP70 and GRP78/BiP can detect and bind misfolded hA oligomers, thereby effectively protecting hA against bulk misfolding and irreversible aggregation. Defective β-cell chaperone biology could contribute to hA misfolding and initiation of apoptosis in T2DM.

scholarly journals Analysis of Amylin Consensus Sequences Suggests That Human Amylin Is Not Optimized to Minimize Amyloid Formation and Provides Clues to Factors That Modulate Amyloidogenicity

2020 ◽  
Vol 15 (6) ◽  
pp. 1408-1416
Author(s):  
Daeun Noh ◽  
Rebekah L. Bower ◽  
Debbie L. Hay ◽  
Alexander Zhyvoloup ◽  
Daniel P. Raleigh
Keyword(s):  
Amyloid Formation ◽  
Consensus Sequences ◽  
Human Amylin

scholarly journals The effects of amylin on carbohydrate metabolism in skeletal muscle in vitro and in vivo

1990 ◽  
Vol 269 (1) ◽  
pp. 19-23 ◽  
Author(s):  
B Leighton ◽  
E Foot
Keyword(s):  
Glucose Utilization ◽  
Glycogen Synthesis ◽  
Intraperitoneal Administration ◽  
Muscle Preparation ◽  
Glucose Incorporation ◽  
Rat Soleus Muscle ◽  
Lactate Formation ◽  
Human Amylin

1. The effects of synthetic human amylin on basal and insulin-stimulated (100 and 1000 microunits/ml) rates of lactate formation, glucose oxidation and glycogen synthesis were measured in the isolated rat soleus muscle preparation incubated in the presence of various concentrations of glucose (5, 11 and 22 mM). 2. The rate of glucose utilization was increased by about 2-fold by increasing the glucose concentration from 5 to 22 mM. 3. Synthetic human amylin (10 nM) significantly inhibited (by 46-56%) glycogen synthesis, irrespective of the concentration of insulin or glucose present in the incubation medium. 4. Amylin (10 nM) did not affect insulin-stimulated rates of 2-deoxy[3H]glucose transport and phosphorylation. 5. Intraperitoneal administration of insulin (100 micrograms/kg) to rats in vivo stimulated the rate of [U-14C]glucose incorporation into glycogen in the diaphragm by about 80-fold. This rate was decreased (by 28%) by co-administration of amylin (66 micrograms/kg).

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