Low generation anionic dendrimers modulate islet amyloid polypeptide self-assembly and inhibit pancreatic β-cell toxicity

RSC Advances ◽  
2016 ◽  
Vol 6 (80) ◽  
pp. 76360-76369 ◽  
Author(s):  
Phuong T. Nguyen ◽  
Rishi Sharma ◽  
Rabindra Rej ◽  
Carole Anne De Carufel ◽  
René Roy ◽  
...  
Keyword(s):  
Self Assembly ◽  
Islet Amyloid Polypeptide ◽  
The Self ◽  
Pancreatic Β Cell ◽  
Cell Toxicity ◽  
Β Cell ◽  
Islet Amyloid

The self-assembly and cytotoxicity of the amyloidogenic peptide IAPP can be controlled with low generation anionic dendrimers.

scholarly journals Pancreatic β-Cell Membrane Fluidity and Toxicity Induced by Human Islet Amyloid Polypeptide Species

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Emily H. Pilkington ◽  
Esteban N. Gurzov ◽  
Aleksandr Kakinen ◽  
Sara A. Litwak ◽  
William J. Stanley ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Membrane Fluidity ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide ◽  
Cell Membrane Fluidity

scholarly journals Identification of a Specific Residue Side Chain Controlling the Self-Assembly and Cytotoxicity of Islet Amyloid Polypeptide

2018 ◽  
Vol 114 (3) ◽  
pp. 77a-78a
Author(s):  
Phuong Trang Nguyen ◽  
Elizabeth Godin ◽  
Ximena Zottig ◽  
Steve Bourgault
Keyword(s):  
Self Assembly ◽  
Islet Amyloid Polypeptide ◽  
The Self ◽  
Side Chain ◽  
Islet Amyloid

New peptide inhibitors modulate the self-assembly of islet amyloid polypeptide residues 11–20 in vitro

2017 ◽  
Vol 804 ◽  
pp. 102-110 ◽  
Author(s):  
Yexuan Mao ◽  
Lanlan Yu ◽  
Ran Yang ◽  
Chuanguo Ma ◽  
Lingbo Qu ◽  
...  
Keyword(s):  
Self Assembly ◽  
Islet Amyloid Polypeptide ◽  
Peptide Inhibitors ◽  
The Self ◽  
Islet Amyloid

Kinetic and Conformational Insights into Islet Amyloid Polypeptide Self-Assembly Using a Biarsenical Fluorogenic Probe

2018 ◽  
Vol 29 (2) ◽  
pp. 517-527 ◽  
Author(s):  
Noé Quittot ◽  
Mathew Sebastiao ◽  
Soultan Al-Halifa ◽  
Steve Bourgault
Keyword(s):  
Self Assembly ◽  
Islet Amyloid Polypeptide ◽  
Islet Amyloid ◽  
Fluorogenic Probe

The potential mechanism of the diabetogenic action of streptozotocin: inhibition of pancreatic β-cell O-GlcNAc-selective N-acetyl-β-d-glucosaminidase

2001 ◽  
Vol 356 (1) ◽  
pp. 31-41 ◽  
Author(s):  
Robert J. KONRAD ◽  
Irina MIKOLAENKO ◽  
Joseph F. TOLAR ◽  
Kan LIU ◽  
Jeffrey E. KUDLOW
Keyword(s):  
Time Course ◽  
Significant Inhibition ◽  
Protein Glycosylation ◽  
Pancreatic Β Cell ◽  
Cell Toxicity ◽  
Β Cells ◽  
Β Cell ◽  
Insulinoma Cell ◽  
Dose Curve ◽  
Insulinoma Cell Line

Streptozotocin (STZ), an analogue of GlcNAc, inhibits purified rat spleen O-GlcNAc-selective N-acetyl-β-d-glucosaminidase (O-GlcNAcase), the enzyme that removes O-GlcNAc from protein. We have shown previously that STZ increases pancreatic islet O-linked protein glycosylation. In light of these data, we investigated the possibility further that STZ causes β-cell death by inhibiting O-GlcNAcase. In isolated islets, the time course and dose curve of STZ-induced O-glycosylation correlated with β-cell toxicity. STZ inhibition of rat islet O-GlcNAcase activity also paralleled that of its β-cell toxicity, with significant inhibition occurring at a concentration of 1mM. In contrast, STZ inhibition of rat brain O-GlcNAcase and β-TC3 insulinoma cell O-GlcNAcase was significantly right-shifted compared with islets, with STZ only significantly inhibiting activity at a concentration of 5mM, the same concentration required for β-TC3 cell toxicity. In comparison, N-methyl-N-nitrosourea, the nitric oxide-donating portion of STZ, did not cause increased islet O-glycosylation, β-cell toxicity or inhibition of β-cell O-GlcNAcase. Enhanced STZ sensitivity of islet O-GlcNAcase compared with O-GlcNAcase from other tissues or an insulinoma cell line suggests why actual islet β-cells are particularly sensitive to STZ. Confirming this idea, STZ-induced islet β-cell toxicity was completely blocked by GlcNAc, which also prevented STZ-induced O-GlcNAcase inhibition, but was not even partially blocked by glucose, glucosamine or GalNAc. Together, these data demonstrate that STZ's inhibition of β-cell O-GlcNAcase is the mechanism that accounts for its diabetogenic toxicity.

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.

scholarly journals β-Cell Dysfunctional ERAD/Ubiquitin/Proteasome System in Type 2 Diabetes Mediated by Islet Amyloid Polypeptide–Induced UCH-L1 Deficiency

Diabetes ◽  
2010 ◽  
Vol 60 (1) ◽  
pp. 227-238 ◽  
Author(s):  
Safia Costes ◽  
Chang-jiang Huang ◽  
Tatyana Gurlo ◽  
Marie Daval ◽  
Aleksey V. Matveyenko ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Islet Amyloid Polypeptide ◽  
Ubiquitin Proteasome System ◽  
Β Cell ◽  
Islet Amyloid ◽  
Ubiquitin Proteasome

Relationship between islet amyloid polypeptide (IAPP) deposition and insulin response and β-cell volume in diabetes mellitus

1992 ◽  
Vol 15 (1) ◽  
pp. 15-16 ◽  
Author(s):  
Tetsuro Kobayashi ◽  
Yuriko Ito ◽  
Koji Nakanish ◽  
Kazuhiko Sugawara ◽  
Minoru Okubo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Volume ◽  
Islet Amyloid Polypeptide ◽  
Insulin Response ◽  
Β Cell ◽  
Islet Amyloid
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