scholarly journals X-Ray Absorption Spectroscopy Measurements of Cu-ProIAPP Complexes at Physiological Concentrations

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.

2019 ◽  
Author(s):  
Wei Ling ◽  
Yi Huang ◽  
Yan-Mei Huang ◽  
Jian Shen ◽  
Shan-Huan Wang ◽  
...  

2002 ◽  
Vol 282 (2) ◽  
pp. E370-E375 ◽  
Author(s):  
Yuval Heled ◽  
Yair Shapiro ◽  
Yoav Shani ◽  
Dani S. Moran ◽  
Lea Langzam ◽  
...  

We hypothesized that exercise training might prevent diabetes mellitus in Psammomys obesus. Animals were assigned to three groups: high-energy diet (CH), high-energy diet and exercise (EH), and low-energy diet (CL). The EH group ran on a treadmill 5 days/wk, twice a day. After 4 wk, 93% of the CH group were diabetic compared with only 20% of the EH group. There was no difference in weight gain among the groups. Both EH and CH groups were hyperinsulinemic. Epididymal fat (% of body weight) was higher in the CH group than in either the EH and or the CL group. Protein kinase C (PKC)-δ activity and serine phosphorylation were higher in the EH group. No differences were found in tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1, and phosphatidylinositol 3-kinase among the groups. We demonstrate for the first time that exercise training effectively prevents the progression of diabetes mellitus type 2 in Psammomys obesus. PKC-δ may be involved in the adaptive effects of exercise in skeletal muscles that lead to the prevention of type 2 diabetes mellitus.


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 ◽  
...  

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 ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Masae Miyatani ◽  
Pearl Yang ◽  
Scott Thomas ◽  
B. Catharine Craven ◽  
Paul Oh

We aimed to compare the level of agreement between leg-to-leg bioelectrical impedance analysis (LBIA) and dual-energy X-ray absorptiometry (DXA) for assessing changes in body composition following exercise intervention among individuals with Type 2 diabetes mellitus (T2DM). Forty-four adults with T2DM, age53.2±9.1years; BMI30.8±5.9 kg/m2participated in a 6-month exercise program with pre and post intervention assessments of body composition. Fat free mass (FFM), % body fat (%FM) and fat mass (FM) were measured by LBIA (TBF-300A) and DXA. LBIA assessments of changes in %FM and FM post intervention showed good relative agreements with DXA variables (P<0.001). However, Bland-Altman plot(s) indicated that there were systematic errors in the assessment of the changes in body composition using LBIA compared to DXA such that, the greater the changes in participant body composition, the greater the disparity in body composition data obtained via LBIA versus DXA data (FFM,P=0.013; %FM,P<0.001; FM,P<0.001). In conclusion, assessment of pre and post intervention body composition implies that LBIA is a good tool for assessment qualitative change in body composition (gain or loss) among people with T2DM but is not sufficiently sensitive to track quantitative changes in an individual’s body composition.


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.


Author(s):  
A. B. Andrusha

Objective — to assess the degree of osteodeficiency and probability of osteoporotic fractures in patients with type 2 diabetes mellitus in the absence or presence of lactase deficiency. Materials and methods. All examined patients with type 2 diabetes mellitus were divided into 2 groups depending on the presence/absence of lactase deficiency. In addition to routine examination methods, specific methods were used for diagnosing lactase deficiency, assessing bone mineral density (using dual‑energy X‑ray absorptiometry) and bone quality (ultrasound densitometry), the state of bone remodelling (according to markers of bone resorption and formation), probability of osteoporotic fractures (using FRAX and QFracture calculators), dietary and lifestyle habits were also studied. Results. The changes have been revealed in both processes of bone remodelling — increased bone resorption and insufficient bone formation, and the activity of bone formation, which was the lowest in patients with lactase deficiency and type 2 diabetes mellitus. The results of X‑ray absorptiometry confirmed that osteoporosis was significantly more often in patients with type 2 diabetes mellitus in the presence of lactase deficiency. The use of ultrasonic densitometry confirmed the violation of bone tissue micro architectonics. The indicator of broadband ultrasound attenuation, which reflects the qualitative characteristics of bone tissue, was the lowest in patients with type 2 diabetes mellitus accompanied by lactase deficiency. The probability of osteoporotic fractures according to the results of the assessment with the online calculator FRAX® was higher than the average risk in both groups of patients. No significant difference was established in this indicator between these groups of patients in contrast to the risk calculated with the QFracture instrument — it was the highest in patients with lactase deficiency. Conclusions. The presence of lactase deficiency in patients with type 2 diabetes mellitus can be considered as a factor that contributes to the development of osteodeficiency, deterioration of the quality of bone tissue, imbalance in bone remodelling and an increase in the probability of osteoporotic fractures.  


Sign in / Sign up

Export Citation Format

Share Document