Pancreatic Vascular Pathologies and Islet Amyloid in Type 2 Diabetes Mellitus

2019 ◽  
Author(s):  
Wei Ling ◽  
Yi Huang ◽  
Yan-Mei Huang ◽  
Jian Shen ◽  
Shan-Huan Wang ◽  
...  
Pancreas ◽  
2020 ◽  
Vol 49 (9) ◽  
pp. 1232-1239
Author(s):  
Wei Ling ◽  
Yi Huang ◽  
Yan-Mei Huang ◽  
Jian Shen ◽  
Shan-Huan Wang ◽  
...  

2011 ◽  
Vol 412 (9-10) ◽  
pp. 785-787 ◽  
Author(s):  
Robert Y.L. Zee ◽  
Patricia Pulido-Perez ◽  
Ricardo Perez-Fuentes ◽  
Paul M Ridker ◽  
Daniel I. Chasman ◽  
...  

2019 ◽  
Vol 4 (1) ◽  
pp. 13 ◽  
Author(s):  
Emiliano De Santis ◽  
Emma Shardlow ◽  
Francesco Stellato ◽  
Olivier Proux ◽  
Giancarlo Rossi ◽  
...  

The amyloidogenic islet amyloid polypeptide (IAPP) and the associated pro-peptide ProIAPP1–48 are involved in cell death in type 2 diabetes mellitus. It has been observed that interactions of this peptide with metal ions have an impact on the cytotoxicity of the peptides as well as on their deposition in the form of amyloid fibrils. In particular, Cu(II) seems to inhibit amyloid fibril formation, thus suggesting that Cu homeostasis imbalance may be involved in the pathogenesis of type 2 diabetes mellitus. We performed X-ray Absorption Spectroscopy (XAS) measurements of Cu(II)-ProIAPP complexes under near-physiological (10 μM), equimolar concentrations of Cu(II) and peptide. Such low concentrations were made accessible to XAS measurements owing to the use of the High Energy Resolved Fluorescence Detection XAS facility recently installed at the ESRF beamline BM16 (FAME-UHD). Our preliminary data show that XAS measurements at micromolar concentrations are feasible and confirm that ProIAPP1–48-Cu(II) binding at near-physiological conditions can be detected.


2016 ◽  
Vol 54 (1) ◽  
pp. 53-61 ◽  
Author(s):  
Rodolfo Guardado-Mendoza ◽  
Alberto O. Chávez ◽  
Lilia M. Jiménez-Ceja ◽  
Andrea Hansis-Diarte ◽  
Ralph A. DeFronzo ◽  
...  

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 116 ◽  
Author(s):  
Elisa S. Roesti ◽  
Christina N. Boyle ◽  
Daniel T. Zeman ◽  
Marcos Sande-Melon ◽  
Federico Storni ◽  
...  

Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by insulin resistance and insufficient insulin secretion to maintain normoglycemia. The majority of T2DM patients bear amyloid deposits mainly composed of islet amyloid polypeptide (IAPP) in their pancreatic islets. These—originally β-cell secretory products—extracellular aggregates are cytotoxic for insulin-producing β-cells and are associated with β-cell loss and inflammation in T2DM advanced stages. Due to the absence of T2DM preventive medicaments and the presence of only symptomatic drugs acting towards increasing hormone secretion and action, we aimed at establishing a novel disease-modifying therapy targeting the cytotoxic IAPP deposits in order to prevent the development of T2DM. We generated a vaccine based on virus-like particles (VLPs), devoid of genomic material, coupled to IAPP peptides inducing specific antibodies against aggregated, but not monomeric IAPP. Using a mouse model of islet amyloidosis, we demonstrate in vivo that our vaccine induced a potent antibody response against aggregated, but not soluble IAPP, strikingly preventing IAPP depositions, delaying onset of hyperglycemia and the induction of the associated pro-inflammatory cytokine Interleukin 1β (IL-1β). We offer the first cost-effective and safe disease-modifying approach targeting islet dysfunction in T2DM, preventing pathogenic aggregates without disturbing physiological IAPP function.


2002 ◽  
Vol 197 (1-2) ◽  
pp. 205-212 ◽  
Author(s):  
Jo W.M Höppener ◽  
Maria G Nieuwenhuis ◽  
Thea M Vroom ◽  
Bo Ahrén ◽  
Cees J.M Lips

2000 ◽  
Vol 343 (6) ◽  
pp. 411-419 ◽  
Author(s):  
Jo W.M. Höppener ◽  
Bo Ahrén ◽  
Cornelis J.M. Lips

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
J. W. M. Höppener ◽  
H. M. Jacobs ◽  
N. Wierup ◽  
G. Sotthewes ◽  
M. Sprong ◽  
...  

Human islet amyloid polypeptide (hIAPP), a pancreatic islet protein of 37 amino acids, is the main component of islet amyloid, seen at autopsy in patients with type 2 diabetes mellitus (DM2). To investigate the roles of hIAPP and islet amyloid in DM2, we generated transgenic mice expressing hIAPP in their islet beta cells. In this study, we found that after a long-term, high-fat diet challenge islet amyloid was observed in only 4 of 19 hIAPP transgenic mice. hIAPP transgenic females exhibited severe glucose intolerance, which was associated with a downregulation of GLUT-2 mRNA expression. In isolated islets from hIAPP males cultured for 3 weeks on high-glucose medium, the percentage of amyloid containing islets increased from 5.5% to 70%. This ex vivo system will allow a more rapid, convenient, and specific study of factors influencing islet amyloidosis as well as of therapeutic strategies to interfere with this pathological process.


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