scholarly journals SENP1-mediated NEMO deSUMOylation in adipocytes limits inflammatory responses and type-1 diabetes progression

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Lan Shao ◽  
Huanjiao Jenny Zhou ◽  
Haifeng Zhang ◽  
Lingfeng Qin ◽  
John Hwa ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Inflammatory Responses ◽  
Diabetes Progression

scholarly journals Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts

2021 ◽  
Author(s):  
Michael G Voss ◽  
David D Cuthbertson ◽  
Mario M Cleves ◽  
Ping Xu ◽  
Carmella Evans-Molina ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetes Prevention ◽  
Prevention Trial ◽  
Oral Glucose ◽  
Z Score ◽  
C Peptide ◽  
Time To Peak ◽  
Diabetes Progression ◽  
Diabetes Development

<b>Objective:</b> To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody positive (Ab+) relatives of people with type 1 diabetes. <p><b>Methods:</b> We examined 2-hour OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (Mean±SD age: 13.84±9.53 years; BMI-Z-Score: 0.33±1.07; 56.1% male) and 3,720 PTP participants (age: 16.01±12.33 Years, BMI-Z-Score 0.66±1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-Score, HOMA-IR and peak Glucose/C-peptide levels, respectively) were performed. </p> <p><b>Results:</b> In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose >30 min and time to peak C-peptide >60 min (p<0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: X<sup>2 </sup>= 25.76 vs. X<sup>2</sup> = 8.62 and PTP: X<sup>2 </sup>= 149.19 vs. X<sup>2</sup> = 79.98; all p<0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time.</p> <p><b>Conclusions: </b>In two independent at risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression. </p>

scholarly journals Higher levels of the soluble receptor for advanced glycation end products and lower levels of the extracellular newly identified receptor for advanced glycation end products were associated with lipid-lowering drugs in patients with type 1 diabetes: a comparative cross-sectional study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Eva O. Melin ◽  
Jonatan Dereke ◽  
Magnus Hillman
Keyword(s):  
Type 1 Diabetes ◽  
Advanced Glycation End Products ◽  
Inflammatory Responses ◽  
Lipid Lowering ◽  
Advanced Glycation ◽  
Cross Sectional ◽  
Lipid Lowering Drugs ◽  
Glycation End Products ◽  
End Products

Abstract Background The receptors for advanced glycation end products (RAGE) are increased in atherosclerotic plaques. Soluble (s)RAGE decreases, whereas the extracellular newly identified receptor for advanced glycation end products (EN-RAGE) increases inflammatory responses mediated by RAGE. The aims were to explore whether sRAGE, EN-RAGE and the EN-RAGE/sRAGE ratio, were associated with the use of lipid-lowering drugs (LLD) and/or antihypertensive drugs (AHD) in patients with type 1 diabetes (T1D). Methods Cross-sectional design. T1D patients were consecutively recruited from one diabetes clinic. Blood samples were collected, supplemented with data from electronic health records. sRAGE and EN-RAGE were analysed by enzyme linked immunosorbent assays. An EN-RAGE/sRAGE ratio was calculated. Adjustments were performed with inflammatory and metabolic variables, s-creatinine, depression, smoking, physical inactivity, medication, and cardiovascular complications. Multiple regression analyses were performed. Results In this study 283 T1D patients (men 56%, 18–59 years) were included. One-hundred and thirty LLD users compared to 153 non-users had lower levels of the EN-RAGE/sRAGE ratio (P = 0.009), and 89 AHD users compared to 194 non-users had lower levels of sRAGE (P = 0.031). The use of LLD (inversely) (B coefficient − 0.158, P = 0.033) and the use of AHD (B coefficient 0.187, P = 0.023) were associated with the EN-RAGE/sRAGE ratio. sRAGE (Lg10) (per unit) (adjusted odds ratio (AOR) = 3.5, 95% CI = 1.4–9.1, P = 0.009), EN-RAGE (Lg10) (per unit) (inversely) (AOR 0.4, 95% CI = 0.2–1.0, P = 0.046), age (P <  0.001), and triglycerides (P <  0.029), were associated with LLD. sRAGE (Lg10) (per unit) (inversely) (AOR = 0.2, 95% CI = 0.1–0.5, P = 0.001), diabetes duration, triglycerides, s-creatinine, and systolic BP (all P values < 0.043), were associated with AHD. Conclusions Higher sRAGE levels and lower EN-RAGE levels were linked to the use of LLD, whereas lower sRAGE levels were linked to the use of AHD. No other variables but the use of LLD and the use of AHD were linked to the EN-RAGE/sRAGE ratio. This may be of major importance as sRAGE is an inhibitor and EN-RAGE is a stimulator of inflammatory processes mediated by RAGE.

scholarly journals Novel Leptin Receptor Mutation in NOD/LtJ Mice Suppresses Type 1 Diabetes Progression: I. Pathophysiological Analysis

Diabetes ◽  
2005 ◽  
Vol 54 (9) ◽  
pp. 2525-2532 ◽  
Author(s):  
C.-H. Lee ◽  
P. C. Reifsnyder ◽  
J. K. Naggert ◽  
C. Wasserfall ◽  
M. A. Atkinson ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Leptin Receptor ◽  
Diabetes Progression

scholarly journals Type 1 diabetes progression is associated with loss of CD3+CD56+ regulatory T cells that control CD8+ T-cell effector functions

2020 ◽  
Vol 2 (2) ◽  
pp. 142-152 ◽  
Author(s):  
Giuseppe Terrazzano ◽  
Sara Bruzzaniti ◽  
Valentina Rubino ◽  
Marianna Santopaolo ◽  
Anna Teresa Palatucci ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd8 T Cell ◽  
Effector Functions ◽  
Diabetes Progression ◽  
Cell Effector

Young adult onset type 2 diabetes versus type 1 diabetes: Progression to and survival on renal replacement therapy

2021 ◽  
pp. 108023
Author(s):  
Timothy L. Middleton ◽  
Steven Chadban ◽  
Lynda Molyneaux ◽  
Mario D'Souza ◽  
Maria I. Constantino ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Renal Replacement Therapy ◽  
Young Adult ◽  
Replacement Therapy ◽  
Adult Onset ◽  
Onset Type ◽  
Diabetes Progression

scholarly journals The Transcription Factor B-Cell Lymphoma (BCL)-6 Modulates Pancreatic β-Cell Inflammatory Responses

Endocrinology ◽  
2010 ◽  
Vol 152 (2) ◽  
pp. 447-456 ◽  
Author(s):  
Mariana Igoillo-Esteve ◽  
Esteban N. Gurzov ◽  
Décio L. Eizirik ◽  
Miriam Cnop
Keyword(s):  
Nitric Oxide ◽  
Type 1 Diabetes ◽  
B Cell ◽  
Inflammatory Responses ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Dependent Manner ◽  
Β Cells ◽  
Β Cell

Abstract Type 1 diabetes is a chronic autoimmune disease with a strong inflammatory component. We have previously shown that expression of the transcriptional repressor B-cell lymphoma (BCL)-6 is very low in pancreatic β-cells, which may favor prolonged proinflammatory responses after exposure to the cytokines IL-1β and interferon γ. Here we investigated whether cytokine-induced inflammation and apoptosis can be prevented in β-cells by BCL-6 expression using plasmid, prolactin, and adenoviral approaches. The induction of mild or abundant BCL-6 expression in β-cells by prolactin or an adenoviral BCL-6 expression construct, respectively, reduced cytokine-induced inflammatory responses in a dose-dependent manner through inhibition of nuclear factor-κB activation. BCL-6 decreased Fas and inducible nitric oxide synthase expression and nitric oxide production, but it inhibited the expression of the antiapoptotic proteins Bcl-2 and JunB while increasing the expression of the proapoptotic death protein 5. The net result of these opposite effects was an augmentation of β-cell apoptosis. In conclusion, BCL-6 expression tones down the unrestrained cytokine-induced proinflammatory response of β-cells but it also favors gene networks leading to apoptosis. This suggests that cytokine-induced proinflammatory and proapoptotic signals can be dissociated in β-cells. Further understanding of these pathways may open new possibilities to improve β-cell survival in early type 1 diabetes or after transplantation.

scholarly journals IFN Regulatory Factors 4 and 8 Expression in the NOD Mouse

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Gilles Besin ◽  
Simon Gaudreau ◽  
Émilie Dumont-Blanchette ◽  
Michael Ménard ◽  
Chantal Guindi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Type 1 Diabetes ◽  
Nod Mice ◽  
Nod Mouse ◽  
Dc Functions ◽  
Gm Csf ◽  
Diabetes Progression ◽  
Islet Inflammation

Dendritic cells (DCs) contribute to islet inflammation and its progression to diabetes in NOD mouse model and human. DCs play a crucial role in the presentation of autoantigen and activation of diabetogenic T cells, and IRF4 and IRF8 are crucial genes involved in the development of DCs. We have therefore investigated the expression of these genes in splenic DCs during diabetes progression in NOD mice. We found that IRF4 expression was upregulated in splenocytes and in splenic CD11c+DCs of NOD mice as compared to BALB/c mice. In contrast, IRF8 gene expression was higher in splenocytes of NOD mice whereas its expression was similar in splenic CD11c+DCs of NOD and BALB/c mice. Importantly, levels of IRF4 and IRF8 expression were lower in tolerogenic bone marrow derived DCs (BMDCs) generated with GM-CSF as compared to immunogenic BMDCs generated with GM-CSF and IL-4. Analysis of splenic DCs subsets indicated that high expression of IRF4 was associated with increased levels of CD4+CD8α−IRF4+CD11c+DCs but not CD4−CD8α+IRF8+CD11c+DCs in NOD mice. Our results showed that IRF4 expression was up-regulated in NOD mice and correlated with the increased levels of CD4+CD8α−DCs, suggesting that IRF4 may be involved in abnormal DC functions in type 1 diabetes in NOD mice.

scholarly journals γ-Aminobutyric Acid Inhibits T Cell Autoimmunity and the Development of Inflammatory Responses in a Mouse Type 1 Diabetes Model

2004 ◽  
Vol 173 (8) ◽  
pp. 5298-5304 ◽  
Author(s):  
Jide Tian ◽  
Yuxin Lu ◽  
Hanwei Zhang ◽  
Cindy H. Chau ◽  
Hoa N. Dang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Inflammatory Responses ◽  
Aminobutyric Acid ◽  
Diabetes Model
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