Photodegradation of porphyrin-bound hIAPP(1–37) fibrils

2020 ◽  
Vol 44 (22) ◽  
pp. 9438-9443
Author(s):  
Yongxiu Song ◽  
Ping Li ◽  
Zhiming Zhang ◽  
Yin Wang ◽  
Zhefei Zhang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Pancreatic Islets ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Preventive Strategy ◽  
Islet Amyloid ◽  
Amyloid Deposits

Amyloid deposits in pancreatic islets of type 2 diabetes mellitus (T2DM) are mainly comprised of human islet amyloid polypeptide (hIAPP), the degradation of hIAPP fibrils by photoactive porphyrin could be a preventive strategy against T2DM.

scholarly journals Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
J. W. M. Höppener ◽  
H. M. Jacobs ◽  
N. Wierup ◽  
G. Sotthewes ◽  
M. Sprong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Transgenic Mice ◽  
Ex Vivo ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Human Islet Amyloid Polypeptide

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.

scholarly journals Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Lucie Caillon ◽  
Anais R. F. Hoffmann ◽  
Alexandra Botz ◽  
Lucie Khemtemourian
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Membrane Damage ◽  
Islet Amyloid Polypeptide ◽  
Amyloid Formation ◽  
Membrane Interactions ◽  
Islet Amyloid ◽  
Amyloid Deposits

Human islet amyloid polypeptide (hIAPP) is the major component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Mature hIAPP, a 37-aa peptide, is natively unfolded in its monomeric state but forms islet amyloid in T2DM. In common with other misfolded and aggregated proteins, amyloid formation involves aggregation of monomers of hIAPP into oligomers, fibrils, and ultimately mature amyloid deposits. hIAPP is coproduced and stored with insulin by the pancreatic isletβ-cells and is released in response to the stimuli that lead to insulin secretion. Accumulating evidence suggests that hIAPP amyloid deposits that accompany T2DM are not just an insignificant phenomenon derived from the disease progression but that hIAPP aggregation induces processes that impair the functionality and the viability ofβ-cells. In this review, we particularly focus on hIAPP structure, hIAPP aggregation, and hIAPP-membrane interactions. We will also discuss recent findings on the mechanism of hIAPP-membrane damage and on hIAPP-induced cell death. Finally, the development of successful antiamyloidogenic agents that prevent hIAPP fibril formation will be examined.

scholarly journals Islet amyloid polypeptide gene variation (IAPP) and the risk of incident type 2 diabetes mellitus: The women's genome health study

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 ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Islet Amyloid Polypeptide ◽  
Health Study ◽  
Islet Amyloid ◽  
Incident Type ◽  
Gene Variation ◽  
Incident Type 2 Diabetes

Islet amyloid polypeptide response to maximal hyperglycemia and arginine is altered in impaired glucose tolerance and type 2 diabetes mellitus

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 ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Islet Amyloid Polypeptide ◽  
Islet Amyloid

scholarly journals Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 116 ◽  
Author(s):  
Elisa S. Roesti ◽  
Christina N. Boyle ◽  
Daniel T. Zeman ◽  
Marcos Sande-Melon ◽  
Federico Storni ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Pancreatic Islets ◽  
Hormone Secretion ◽  
Β Cell ◽  
Islet Amyloid ◽  
Disease Modifying

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.

PEG modified graphene oxide loaded with EALYLV peptides for inhibiting the aggregation of hIAPP associated with type-2 diabetes

2015 ◽  
Vol 3 (35) ◽  
pp. 7055-7067 ◽  
Author(s):  
Xianbo Zhou ◽  
Chengwen Cao ◽  
Qingchang Chen ◽  
Qianqian Yu ◽  
Yanan Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Graphene Oxide ◽  
Pancreatic Islets ◽  
Islet Amyloid Polypeptide ◽  
Human Islet ◽  
Islet Amyloid ◽  
Amyloid Aggregate ◽  
Modified Graphene Oxide ◽  
Modified Graphene

Human islet amyloid polypeptide (hIAPP) was found as amyloid aggregate deposits in the pancreatic islets of patients with type-2 diabetes and studies showed that insulin and its derivatives were the potent inhibitors of hIAPP aggregation.

scholarly journals Recent Insights in Islet Amyloid Polypeptide-Induced Membrane Disruption and Its Role inβ-Cell Death in Type 2 Diabetes Mellitus

2008 ◽  
Vol 2008 ◽  
pp. 1-9 ◽  
Author(s):  
Lucie Khemtémourian ◽  
J. Antoinette Killian ◽  
Jo W. M. Höppener ◽  
Maarten F. M. Engel
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cell Death ◽  
Type 2 Diabetes Mellitus ◽  
Membrane Damage ◽  
Islet Amyloid Polypeptide ◽  
Islet Amyloid ◽  
Induced Membrane ◽  
Pancreatic Islets Of Langerhans

The presence of fibrillar protein deposits (amyloid) of human islet amyloid polypeptide (hIAPP) in the pancreatic islets of Langerhans is thought to be related to death of the insulin-producing isletβ-cells in type 2 diabetes mellitus (DM2). The mechanism of hIAPP-inducedβ-cell death is not understood. However, there is growing evidence that hIAPP-induced disruption ofβ-cell membranes is the cause of hIAPP cytotoxicity. Amyloid cytotoxicity by membrane damage has not only been suggested for hIAPP, but also for peptides and proteins related to other misfolding diseases, like Alzheimer’s disease, Parkinson’s disease, and prion diseases. Here we review the interaction of hIAPP with membranes, and discuss recent progress in the field, with a focus on hIAPP structure and on the proposed mechanisms of hIAPP-induced membrane damage in relation toβ-cell death in DM2.

scholarly journals Association of Islet Amyloid Polypeptide and Inflammatory Markers in Type 2 Diabetes Mellitus

2021 ◽  
Author(s):  
Zunjarrao Ganpat Badade ◽  
Yogita Mahendra Shinde ◽  
Shibban K Kaul ◽  
Sandeep Rai ◽  
Sameer Kadam
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Sensitivity ◽  
Inflammatory Markers ◽  
Islet Amyloid Polypeptide ◽  
Islet Amyloid ◽  
Tnf Α ◽  
Inflammatory Processes

Introduction: Islet Amyloid Polypeptide (IAPP) is co-synthesised and co-secreted with insulin by islets of pancreatic β-cells, its increased concentration in individuals with type 2 diabetes mellitus, may involve in inflammatory processes. Aim: To study and find the association of IAPP with inflammatory markers including high-sensitivity C-reactive protein (hsCRP), Tumor Necrosis Factor (TNF)-a and Interleukin(IL)-6 in patients with type 2 diabetes mellitus. Materials and Methods: This was a cross-sectional study, conducted from, December 2015 to December 2019, on 262 subjects (30-60 years, 147 males and 115 females), including 131 healthy controls and 131 known cases of type 2 diabetes mellitus, Fasting blood glucose and glycated haemoglobin(HbA1c) was estimated by commercially available kit, and serum fasting insulin, IAPP, hsCRP, TNF-α, and IL-6 were analysed by ELISA. Insulin Resistance (IR) and insulin sensitivity were calculated. Statistical analysis was done with Statistical Package Social Sciences (SPSS) version 24 the descriptive statistics were expressed as Mean±SD, Student t-test was applied, and p≤0.05 was considered as statistically significant and highly significant at ≤0.01 at 95% CI. The relationship between IAPP and other variables were done by using Spearman Rank correlation (r). Results: Circulatory level of IAPP was positively associated with serum hsCRP (r=0.312, p≤0.05) in type 2 diabetes mellitus. The elevated levels of IAPP (21.3±10.54pmol/l), insulin (11.74±3.91μU/ml), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (5.11±2.01) and inflammatory markers including hsCRP (3.44±1.77mg/l), TNF-α (29.5±4.7pg/ml) and IL-6 (20.2±5.2pg/ml) p≤0.05 with poor glycaemic control (HbA1c 8.78±2.30%, p<0.001), and reduced insulin sensitivity {Quantitative Insulin Sensitivity Check Index (QUICKI) 0.31±0.02, p≤0.05} were compared with healthy control; indicates that hyperamylinemia may induce inflammation in individuals with T2DM. Conclusion: Elevated degree of IAPP can be an important predictor and indicator of inflammatory processes and IR in uncontrolled diabetes.

Sign in / Sign up

Export Citation Format

Share Document