Resveratrol attenuates hIAPP amyloid formation and restores the insulin secretion ability in hIAPP-INS1 cell line via enhancing autophagy

2019 ◽  
Vol 97 (2) ◽  
pp. 82-89 ◽  
Author(s):  
Wu Lv ◽  
Jialin Zhang ◽  
Ao Jiao ◽  
Bowen Wang ◽  
Baomin Chen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Cell Line ◽  
Islet Transplantation ◽  
Pancreatic Beta Cells ◽  
Chemical Structure ◽  
Amyloid Deposition ◽  
Amyloid Formation ◽  
Islet Amyloid

It has been proved that human islet amyloid polypeptide (hIAPP), the main constituent of islet amyloid deposition, is one of the important factors that can induce type 2 diabetes or graft failure after islet transplantation. As there is no research on whether resveratrol degrading the amyloid deposition by its special chemical structure or enhancing autophagy had been published, we decided to detect the function of resveratrol in degrading the amyloid deposition in pancreatic beta cells. We established stable hIAPP-INS1 cell line via transfecting INS1 cells by lentivirus that overexpresses hIAPP. Our research demonstrates that amyloid deposition existed in hIAPP-INS1 cell by the thioflavin S fluorescent staining, meanwhile the function of insulin secretion of hIAPP-INS1 cells was decreased significantly (p < 0.01). After treatment with resveratrol (20 μM) for 24 h, amyloid deposition in hIAPP-INS1 cells was decreased significantly, and the insulin secretion was restored significantly (p < 0.01). Once inhibited the autophagy of hIAPP-INS1 cells by 3-methyladenine for 24 h, resveratrol does not effectively remove hIAPP deposits again, and cannot improve the function of insulin secretion. These results provide a novel thought that resveratrol can degrade the amyloid deposition in type 2 diabetes and the graft after islet transplantation.

Dual role of interleukin-1β in islet amyloid formation and its β-cell toxicity: Implications for type 2 diabetes and islet transplantation

2017 ◽  
Vol 19 (5) ◽  
pp. 682-694 ◽  
Author(s):  
Yoo Jin Park ◽  
Garth L. Warnock ◽  
Ziliang Ao ◽  
Nooshin Safikhan ◽  
Mark Meloche ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Islet Transplantation ◽  
Dual Role ◽  
Interleukin 1Β ◽  
Amyloid Formation ◽  
Cell Toxicity ◽  
Β Cell ◽  
Islet Amyloid

scholarly journals Molecular Docking Studies of Possible Treatment of Diabetes using Vasicine against Islet Amyloid Polypeptide

2021 ◽  
Vol 9 (VI) ◽  
pp. 4202-4209
Author(s):  
Tushar Kumar
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Molecular Docking ◽  
Islet Amyloid Polypeptide ◽  
Docking Studies ◽  
Islet Amyloid ◽  
Molecular Docking Studies ◽  
The World ◽  
Treatment Of Diabetes

Diabetes is the becoming one of the most common problem all over the world. About 1 in 10 persons are suffering from diabetes and most from type 2 diabetes. It occurs due to problem in pancreas which further results defect in the insulin secretion, as insulin maintains blood glucose level. The effect of Alpha-Amyrin Acetate, Myrcene and Vasicine compounds against Islet Amyloid polypeptide (IAPP) protein was seen through molecular docking studies. IAPP acts as complementary to insulin in regulating the sugar level for the treatment of diabetes disease by virtual screening. Different tools and software used in this research were Uniprot, Pubchem, Swiss ADMS, PyRx, Auto dock Vina/MGL tool and PyMOL.

scholarly journals β-Cell Loss and β-Cell Apoptosis in Human Type 2 Diabetes Are Related to Islet Amyloid Deposition

2011 ◽  
Vol 178 (6) ◽  
pp. 2632-2640 ◽  
Author(s):  
Catherine A. Jurgens ◽  
Mirna N. Toukatly ◽  
Corinne L. Fligner ◽  
Jayalakshmi Udayasankar ◽  
Shoba L. Subramanian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Apoptosis ◽  
Cell Loss ◽  
Amyloid Deposition ◽  
Β Cell ◽  
Islet Amyloid ◽  
Human Type

Islet Amyloid in Patients With Diabetes Due to Exocrine Pancreatic Disorders, Type 2 Diabetes, and Nondiabetic Patients

2020 ◽  
Vol 105 (8) ◽  
pp. 2595-2605
Author(s):  
Sandra Ueberberg ◽  
Michael A Nauck ◽  
Waldemar Uhl ◽  
Chiara Montemurro ◽  
Andrea Tannapfel ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Pancreatic Tissue ◽  
Amyloid Formation ◽  
Β Cell ◽  
Islet Amyloid ◽  
Amyloid Deposits ◽  
Typical Finding ◽  
Patients With Diabetes ◽  
Pancreatic Disorders

Abstract Background Amyloid deposits are a typical finding in pancreatic islets from patients with type 2 diabetes. Whether this is linked to the pathogenesis of type 2 diabetes is currently unknown. Therefore, we compared the occurrence of islet amyloid in patients with type 2 diabetes, diabetes secondary to pancreatic disorders, and nondiabetic individuals. Patients and methods Pancreatic tissue from 15 nondiabetic patients, 22 patients with type 2 diabetes, and 11 patients with diabetes due to exocrine pancreatic disorders (chronic pancreatitis, pancreatic carcinoma) were stained for insulin, amyloid, and apoptosis. β-cell area, amyloid deposits, and β-cell apoptosis were quantified by morphometric analysis. Results The proportion of islets containing amyloid deposits was significantly higher in both type 2 diabetes and diabetes due to exocrine pancreatic disorders than in healthy subjects. Islets with both amyloid and apoptosis were observed more frequently in type 2 diabetes and significantly more so in diabetes due to exocrine pancreatic disorders. In both diabetic groups, apoptotic ß-cells were found significantly more frequently in islets with more prominent amyloid deposits. Conclusions The occurrence of amyloid deposits in both type 2 diabetes and diabetes secondary to exocrine pancreatic disorders suggests that islet amyloid formation is a common feature of diabetes mellitus of different etiologies and may be associated with a loss of pancreatic ß-cells.

scholarly journals Amyloid damage to islet β-cells in type 2 diabetes: hypoxia or pseudo-hypoxia?

2019 ◽  
Author(s):  
Vittorio Bellotti ◽  
Alessandra Corazza ◽  
Beatrice Foglia ◽  
Erica Novo ◽  
J. Paul Simons ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amyloid Deposition ◽  
Β Cells ◽  
Islet Amyloid ◽  
Good Tool ◽  
Amyloid Deposits ◽  
Oxygen Perfusion

ABSTRACTAggregation of islet amyloid polypeptide (IAPP) and amyloid deposition in the islets of Langerhans may significantly contribute to the multifactorial pathogenic mechanisms leading to type 2 diabetes. A direct toxic effect on β-cells of oligomeric IAAP has been demonstrated in in vitro models, but the mechanism operating in vivo is still unclear. Mice models presenting amyloid deposition and glucose intolerance represent a good tool for exploring in vivo a putative mechanism of toxicity directly related to the physical expansion of the extracellular matrix by the amyloid fibrillar aggregates. Based on our hypothesis that deposition of amyloid may influence the oxygen perfusion, we have calculated that the mean distribution of oxygen partial pressure would drop by more than 50 % in the presence of amyloid deposits in the islet. This condition of hypoxia caused by the remodelling of the extracellular space may explain the metabolic abnormalities in the Langerhans islets, otherwise interpreted as pseudo-hypoxic response to IAPP oligomers.

scholarly journals Exocytosis mechanisms underlying insulin release and glucose uptake: conserved roles for Munc18c and syntaxin 4

2010 ◽  
Vol 298 (3) ◽  
pp. R517-R531 ◽  
Author(s):  
Jenna L. Jewell ◽  
Eunjin Oh ◽  
Debbie C. Thurmond
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Uptake ◽  
Pancreatic Beta Cells ◽  
Insulin Action ◽  
Molecular Mechanisms ◽  
Receptor Protein ◽  
Peripheral Tissues ◽  
Syntaxin 4

Type 2 diabetes has been coined “a two-hit disease,” as it involves specific defects of glucose-stimulated insulin secretion from the pancreatic beta cells in addition to defects in peripheral tissue insulin action required for glucose uptake. Both of these processes, insulin secretion and glucose uptake, are mediated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein core complexes composed of syntaxin, SNAP-23/25, and VAMP proteins. The SNARE core complex is regulated by the Sec1/Munc18 (SM) family of proteins, which selectively bind to their cognate syntaxin isoforms with high affinity. The process of insulin secretion uses multiple Munc18-syntaxin isoform pairs, whereas insulin action in the peripheral tissues appears to use only the Munc18c-syntaxin 4 pair. Importantly, recent reports have linked obesity and Type 2 diabetes in humans with changes in protein levels and single nucleotide polymorphisms (SNPs) of Munc18 and syntaxin isoforms relevant to these exocytotic processes, although the molecular mechanisms underlying the observed phenotypes remain incomplete ( 5 , 104 , 144 ). Given the conservation of these proteins in two seemingly disparate processes and the need to design and implement novel and more effective clinical interventions, it will be vitally important to delineate the mechanisms governing these conserved SNARE-mediated exocytosis events. Thus, we provide here an up-to-date historical review of advancements in defining the roles and molecular mechanisms of Munc18-syntaxin complexes in the pathophysiology of Type 2 diabetes.

scholarly journals Stabilization and structural analysis of a membrane-associated hIAPP aggregation intermediate

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Diana C Rodriguez Camargo ◽  
Kyle J Korshavn ◽  
Alexander Jussupow ◽  
Kolio Raltchev ◽  
David Goricanec ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Death ◽  
Islet Amyloid Polypeptide ◽  
Amyloid Β ◽  
Md Simulations ◽  
Human Islet ◽  
Amyloid Formation ◽  
Islet Amyloid ◽  
Induce Cell Death

Membrane-assisted amyloid formation is implicated in human diseases, and many of the aggregating species accelerate amyloid formation and induce cell death. While structures of membrane-associated intermediates would provide tremendous insights into the pathology and aid in the design of compounds to potentially treat the diseases, it has not been feasible to overcome the challenges posed by the cell membrane. Here, we use NMR experimental constraints to solve the structure of a type-2 diabetes related human islet amyloid polypeptide intermediate stabilized in nanodiscs. ROSETTA and MD simulations resulted in a unique β-strand structure distinct from the conventional amyloid β-hairpin and revealed that the nucleating NFGAIL region remains flexible and accessible within this isolated intermediate, suggesting a mechanism by which membrane-associated aggregation may be propagated. The ability of nanodiscs to trap amyloid intermediates as demonstrated could become one of the most powerful approaches to dissect the complicated misfolding pathways of protein aggregation.

Apolipoprotein E genotype, islet amyloid deposition and severity of Type 2 diabetes

2003 ◽  
Vol 60 (2) ◽  
pp. 105-110 ◽  
Author(s):  
D.S Powell ◽  
H Maksoud ◽  
S.B.P Chargé ◽  
J.H Moffitt ◽  
M Desai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Apolipoprotein E ◽  
Amyloid Deposition ◽  
Islet Amyloid ◽  
Apolipoprotein E Genotype

scholarly journals RNA-seq-based identification of Star upregulation by islet amyloid formation

2019 ◽  
Vol 32 (2) ◽  
pp. 67-76 ◽  
Author(s):  
Meghan F Hogan ◽  
Mark Ziemann ◽  
Harikrishnan K N ◽  
Hanah Rodriguez ◽  
Antony Kaspi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Regulatory Protein ◽  
Amyloid Formation ◽  
Rna Seq ◽  
Islet Amyloid ◽  
Gene Sets ◽  
Lipids Metabolism ◽  
Steroidogenic Acute Regulatory

AbstractAggregation of islet amyloid polypeptide (IAPP) into islet amyloid results in β-cell toxicity in human type 2 diabetes. To determine the effect of islet amyloid formation on gene expression, we performed ribonucleic acid (RNA) sequencing (RNA-seq) analysis using cultured islets from either wild-type mice (mIAPP), which are not amyloid prone, or mice that express human IAPP (hIAPP), which develop amyloid. Comparing mIAPP and hIAPP islets, 5025 genes were differentially regulated (2439 upregulated and 2586 downregulated). When considering gene sets (reactomes), 248 and 52 pathways were up- and downregulated, respectively. Of the top 100 genes upregulated under two conditions of amyloid formation, seven were common. Of these seven genes, only steroidogenic acute regulatory protein (Star) demonstrated no effect of glucose per se to modify its expression. We confirmed this differential gene expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and also demonstrated the presence of STAR protein in islets containing amyloid. Furthermore, Star is a part of reactomes representing metabolism, metabolism of lipids, metabolism of steroid hormones, metabolism of steroids and pregnenolone biosynthesis. Thus, examining gene expression that is differentially regulated by islet amyloid has the ability to identify new molecules involved in islet physiology and pathology applicable to type 2 diabetes.

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