scholarly journals 173. Insulin B9-23 LV-Driven Expression in Hepatocytes Combined With Suboptimal Dose of Anti-CD3 mAb Cures Type 1 Diabetes in NOD Mice

2015 ◽  
Vol 23 ◽  
pp. S69
Author(s):  
Andrea Annoni ◽  
Fabio Russo ◽  
Alessio Cantore ◽  
Luigi Naldini ◽  
Maria Grazia Roncarolo
Keyword(s):  
Type 1 Diabetes ◽  
Nod Mice ◽  
Suboptimal Dose

scholarly journals GABAB-Receptor Agonist-Based Immunotherapy for Type 1 Diabetes in NOD Mice

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 43
Author(s):  
Jide Tian ◽  
Blake Middleton ◽  
Victoria Seunghee Lee ◽  
Hye Won Park ◽  
Zhixuan Zhang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gabab Receptor ◽  
Combined Treatment ◽  
Nod Mice ◽  
Rna Seq ◽  
Gaba Production ◽  
Insulin Cells ◽  
Suboptimal Dose ◽  
Clinical Potential

Some immune system cells express type A and/or type B γ-aminobutyric acid receptors (GABAA-Rs and/or GABAB-Rs). Treatment with GABA, which activates both GABAA-Rs and GABAB-Rs), and/or a GABAA-R-specific agonist inhibits disease progression in mouse models of type 1 diabetes (T1D), multiple sclerosis, rheumatoid arthritis, and COVID-19. Little is known about the clinical potential of specifically modulating GABAB-Rs. Here, we tested lesogaberan, a peripherally restricted GABAB-R agonist, as an interventive therapy in diabetic NOD mice. Lesogaberan treatment temporarily restored normoglycemia in most newly diabetic NOD mice. Combined treatment with a suboptimal dose of lesogaberan and proinsulin/alum immunization in newly diabetic NOD mice or a low-dose anti-CD3 in severely hyperglycemic NOD mice greatly increased T1D remission rates relative to each monotherapy. Mice receiving combined lesogaberan and anti-CD3 displayed improved glucose tolerance and, unlike mice that received anti-CD3 alone, had some islets with many insulin+ cells, suggesting that lesogaberan helped to rapidly inhibit β-cell destruction. Hence, GABAB-R-specific agonists may provide adjunct therapies for T1D. Finally, the analysis of microarray and RNA-Seq databases suggested that the expression of GABAB-Rs and GABAA-Rs, as well as GABA production/secretion-related genes, may be a more common feature of immune cells than currently recognized.

1190-P: IFN-Alpha Kinoid: A Promising Vaccine against Type 1 Diabetes Targeting IFN-alpha in NOD Mice

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1190-P
Author(s):  
NOÉMIE CAILLOT ◽  
FABIEN COLAONE ◽  
ROMAIN BERTRAND ◽  
JENNIFER DA SILVA ◽  
SAMIR HAMDI ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nod Mice ◽  
Ifn Alpha

PBI-4547 Prevents Progression of Prediabetic Condition to Type 1 Diabetes in NOD Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1817-P
Author(s):  
FRANÇOIS A. LEBLOND ◽  
KATHY HINCE ◽  
FRANÇOIS SARRA-BOURNET ◽  
WILLIAM GAGNON ◽  
MIKAËL TREMBLAY ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nod Mice

A Novel Dual-Function GLP-1 Analogue Prevents Type 1 Diabetes Onset in NOD Mice by Controlling the Balance of Treg/Th17 and Th2/Th1

2019 ◽  
Author(s):  
Fujian Qin ◽  
Yanfeng Zhang ◽  
Kaiying Li ◽  
Huashan Gao ◽  
Qian Zhao ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nod Mice ◽  
Dual Function ◽  
Diabetes Onset

scholarly journals MBD2 acts as a repressor to maintain the homeostasis of the Th1 program in type 1 diabetes by regulating the STAT1-IFN-γ axis

2021 ◽  
Author(s):  
Tiantian Yue ◽  
Fei Sun ◽  
Faxi Wang ◽  
Chunliang Yang ◽  
Jiahui Luo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Type 1 Diabetes ◽  
Adoptive Transfer ◽  
Nod Mice ◽  
Transcriptional Level ◽  
Clinical Settings ◽  
Cpg Dna ◽  
Ifn Γ

AbstractThe methyl-CpG-binding domain 2 (MBD2) interprets DNA methylome-encoded information through binding to the methylated CpG DNA, by which it regulates target gene expression at the transcriptional level. Although derailed DNA methylation has long been recognized to trigger or promote autoimmune responses in type 1 diabetes (T1D), the exact role of MBD2 in T1D pathogenesis, however, remains poorly defined. Herein, we generated an Mbd2 knockout model in the NOD background and found that Mbd2 deficiency exacerbated the development of spontaneous T1D in NOD mice. Adoptive transfer of Mbd2−/− CD4 T cells into NOD.scid mice further confirmed the observation. Mechanistically, Th1 stimulation rendered the Stat1 promoter to undergo a DNA methylation turnover featured by the changes of DNA methylation levels or patterns along with the induction of MBD2 expression, which then bound to the methylated CpG DNA within the Stat1 promoter, by which MBD2 maintains the homeostasis of Th1 program to prevent autoimmunity. As a result, ectopic MBD2 expression alleviated CD4 T cell diabetogenicity following their adoptive transfer into NOD.scid mice. Collectively, our data suggest that MBD2 could be a viable target to develop epigenetic-based therapeutics against T1D in clinical settings.

scholarly journals IRAK-M Deficiency Promotes the Development of Type 1 Diabetes in NOD Mice

Diabetes ◽  
2014 ◽  
Vol 63 (8) ◽  
pp. 2761-2775 ◽  
Author(s):  
Q. Tan ◽  
M. Majewska-Szczepanik ◽  
X. Zhang ◽  
M. Szczepanik ◽  
Z. Zhou ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Nod Mice

OR.23. Interferon Alpha Initiates Type 1 Diabetes in NOD Mice

2008 ◽  
Vol 127 ◽  
pp. S11
Author(s):  
Qing Li ◽  
Baohui Xu ◽  
Kathleen Rubins ◽  
Sara Michie ◽  
Robert Schreiber ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Interferon Alpha ◽  
Nod Mice

scholarly journals Sphingosine-1-phosphate inhibits high glucose-mediated ERK1/2 action in endothelium through induction of MAP kinase phosphatase-3

2009 ◽  
Vol 296 (2) ◽  
pp. C339-C345 ◽  
Author(s):  
Angela M. Whetzel ◽  
David T. Bolick ◽  
Catherine C. Hedrick
Keyword(s):  
Endothelial Cells ◽  
Type 1 Diabetes ◽  
Vascular Complications ◽  
Nod Mice ◽  
Endothelial Activation ◽  
Adhesion Assay ◽  
Monocyte Adhesion ◽  
Map Kinase Phosphatase ◽  
Sphingosine 1 Phosphate

Endothelial activation is a key early event in vascular complications of Type 1 diabetes. The nonobese diabetic (NOD) mouse is a well-characterized model of Type 1 diabetes. We previously reported that Type 1 diabetic NOD mice have increased endothelial activation, with increased production of monocyte chemoattractant protein (MCP)-1 and IL-6, and a 30% increase of surface VCAM-1 expression leading to a fourfold increase in monocyte adhesion to the endothelium. Sphingosine-1-phosphate (S1P) prevents monocyte:endothelial interactions in these diabetic NOD mice. Incubation of diabetic NOD endothelial cells (EC) with S1P (100 nmol/l) reduced ERK1/2 phosphorylation by 90%, with no significant changes in total ERK1/2 protein. In the current study, we investigated the mechanism of S1P action on ERK1/2 to reduce activation of diabetic endothelium. S1P caused a significant threefold increase in mitogen-activated kinase phosphatase-3 (MKP-3) expression in EC. MKP-3 selectively regulates ERK1/2 activity through dephosphorylation. Incubation of diabetic NOD EC with S1P and the S1P1-selective agonist SEW2871 significantly increased expression of MKP-3 and reduced ERK1/2 phosphorylation, while incubation with the S1P1/S1P3 antagonist VPC23019 decreased the expression of MKP-3, both results supporting a role for S1P1 in MKP-3 regulation. To mimic the S1P-mediated induction of MKP-3 diabetic NOD EC, we overexpressed MKP-3 in human aortic endothelial cells (HAEC) cultured in elevated glucose (25 mmol/l). Overexpression of MKP-3 in glucose-cultured HAEC decreased ERK1/2 phosphorylation and resulted in decreased monocyte:endothelial interactions in a static monocyte adhesion assay. Finally, we used small interfering RNA to MKP-3 and observed increased monocyte adhesion. Moreover, S1P was unable to inhibit monocyte adhesion in the absence of MKP-3. Thus, one mechanism for the anti-inflammatory action of S1P in diabetic EC is inhibition of ERK1/2 phosphorylation through induction of MKP-3 expression via the S1P-S1P1 receptor axis.

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