scholarly journals Anti-inflammatory and antioxidant potential capacities of AD-MSCs and BM-MSCs in suppressing pancreatic β-cells auto-immunity and apoptosis in rats with T1DM induced model

BIOCELL ◽  
2022 ◽  
Vol 46 (3) ◽  
pp. 745-757
Author(s):  
SHADY G. EL-SAWAH ◽  
FAYEZ ALTHOBAITI ◽  
HANAN M. RASHWAN ◽  
ADIL ALDHAHRANI ◽  
MARWA A. ABDEL-DAYEM ◽  
...  
Keyword(s):  
Antioxidant Potential ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Anti Inflammatory

PPARγ is not required for the inhibitory actions of PGJ2 on cytokine signaling in pancreatic β-cells

2004 ◽  
Vol 286 (3) ◽  
pp. E329-E336 ◽  
Author(s):  
Sarah M. Weber ◽  
Anna L. Scarim ◽  
John A. Corbett
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Cytokine Signaling ◽  
Rinm5f Cells ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Inos Gene ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Inos Gene Expression

Peroxisome proliferator-activated receptor (PPAR)γ agonists, such as 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2) and troglitazone, have been shown to elicit anti-inflammatory effects in pancreatic β-cells that include inhibition of cytokine-stimulated inducible nitric oxide synthase (iNOS) gene expression and production of nitric oxide. In addition, these ligands impair IL-1-induced NF-κB and MAPK as well as IFN-γ-stimulated signal transducer and activator of transcription (STAT)1 activation in β-cells. The purpose of this study was to determine if PPARγ activation participates in the anti-inflammatory actions of PGJ2 in β-cells. Pretreatment of RINm5F cells for 6 h with PGJ2 results in inhibition of IL-1-stimulated IκB degradation and IFN-γ-stimulated STAT1 phosphorylation. Overexpression of a dominant-negative (dn) PPARγ mutant or treatment with the PPARγ antagonist GW-9662 does not modulate the inhibitory actions of PGJ2 on cytokine signaling in RINm5F cells. Although these agents fail to attenuate the inhibitory actions of PGJ2 on cytokine signaling, they do inhibit PGJ2-stimulated PPARγ response element reporter activity. Consistent with the inability to attenuate the inhibitory actions of PGJ2 on cytokine signaling, neither dnPPARγ nor GW-9662 prevents the inhibitory actions of PGJ2 on IL-1-stimulated iNOS gene expression or nitric oxide production by RINm5F cells. These findings support a PPARγ-independent mechanism by which PPARγ ligands impair cytokine signaling and iNOS expression by islets.

scholarly journals Mechanisms of Artemisia scoparia ’s Anti‐Inflammatory Activity in Cultured Adipocytes, Macrophages, and Pancreatic β‐Cells

Obesity ◽  
2020 ◽  
Vol 28 (9) ◽  
pp. 1726-1735
Author(s):  
Anik Boudreau ◽  
Susan J. Burke ◽  
J. Jason Collier ◽  
Allison J. Richard ◽  
David M. Ribnicky ◽  
...  
Keyword(s):  
Inflammatory Activity ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Artemisia Scoparia ◽  
Anti Inflammatory

PPARγ ligands induce ER stress in pancreatic β-cells: ER stress activation results in attenuation of cytokine signaling

2004 ◽  
Vol 287 (6) ◽  
pp. E1171-E1177 ◽  
Author(s):  
Sarah M. Weber ◽  
Kari T. Chambers ◽  
Kenneth G. Bensch ◽  
Anna L. Scarim ◽  
John A. Corbett
Keyword(s):  
Er Stress ◽  
Protective Action ◽  
Protein Translation ◽  
Initiation Factor ◽  
Cytokine Signaling ◽  
Peroxisome Proliferator ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Anti Inflammatory ◽  
Stress Activation

Peroxisome proliferator-activated receptor (PPAR)γ ligands are known to have anti-inflammatory properties that include the inhibition of cytokine signaling, transcription factor activation, and inflammatory gene expression. We have recently observed that increased expression of heat shock protein (HSP)70 correlates with, but is not required for, the anti-inflammatory actions of PPARγ ligands on cytokine signaling. In this study, we provide evidence that the inhibitory actions of PPARγ ligands on cytokine signaling are associated with endoplasmic reticulum (ER) stress or unfolded protein response (UPR) activation in pancreatic β-cells. 15-Deoxy-Δ12,14-prostaglandin J2, at concentrations that inhibit cytokine signaling, stimulates phosphorylation of eukaryotic initiation factor-2α, and this event is followed by a rapid inhibition of protein translation. Under conditions of impaired translation, PPARγ ligands stimulate the expression of a number of ER stress-responsive genes, such as GADD 153, BiP, and HSP70. Importantly, ER stress activation in response to PPARγ ligands or known UPR activators results in the attenuation of IL-1 and IFN-γ signaling. These findings indicate that PPARγ ligands induce ER stress, that ER stress activation is associated with an attenuation of cytokine signaling in β-cells, and that the attenuation of responsiveness to extracellular stimuli appears to be a novel protective action of the UPR in cells undergoing ER stress.

MICROCHEMICAL ASSAYS OF GLUCOSE AND GLUCOSE-6-PHOSPHATE IN MAMMALIAN PANCREATIC β-CELLS

1968 ◽  
Vol 59 (3) ◽  
pp. 479-486 ◽  
Author(s):  
Lars-Ake Idahl ◽  
Bo Hellman
Keyword(s):  
Glucose Level ◽  
Exocrine Pancreas ◽  
The Other ◽  
Wide Concentration Range ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Enzymatic Cycling ◽  
Glucose Diffusion ◽  
Significant Barrier ◽  
The Brain

ABSTRACT The combination of enzymatic cycling and fluorometry was used for measuring glucose and glucose-6-phosphate in pancreatic β-cells from obese-hyperglycaemic mice. The glucose level of the β-cells corresponded to that of serum over a wide concentration range. In the exocrine pancreas, on the other hand, a significant barrier to glucose diffusion across the cell membranes was demonstrated. During 5 min of ischaemia, the glucose level remained practically unchanged in the β-cells while it increased in the liver and decreased in the brain. The observation that the pancreatic β-cells are characterized by a relatively low ratio of glucose-6-phosphate to glucose may be attributed to the presence of a specific glucose-6-phosphatase.

Design and Synthesis of Novel Anti-inflammatory/Anti-ulcer Hybrid Molecules with Antioxidant Activity

2020 ◽  
Vol 16 ◽  
Author(s):  
Bhim Bahadur Chaudhari ◽  
Alka Bali ◽  
Ajitesh Balaini
Keyword(s):  
Antioxidant Activity ◽  
Oral Absorption ◽  
Radical Scavenging ◽  
Reducing Power ◽  
Antioxidant Potential ◽  
Inflammatory Activity ◽  
In Vivo Models ◽  
Standard Drug ◽  
Hybrid Molecules ◽  
Anti Inflammatory

Background: NSAIDs are the most widely prescribed medications worldwide for their anti-inflammatory, antipyretic, and analgesic effects However, their chronic use can lead to several adverse drug events including GI toxicity. The selective COX-2 inhibitors developed as gastro-sparing NSAIDs also suffer from serious adverse effects which limit their efficacy. Objective: Local generation of reactive oxygen species is implicated in NSAID-mediated gastric ulceration and their combination with H2 antagonists like famotidine reduces the risk of ulcers. The objective of this work was to design and synthesize novel methanesulphonamido isoxazole derivatives by hybridizing the structural features of NSAIDs with those of antiulcer drugs (ranitidine, famotidine, etc.) to utilize a dual combination of anti-inflammatory activity and reducing (antioxidant) potential. Method: The designing process utilized three dimensional similarity studies and utilized an isoxazole core having a potential for anti-inflammatory as well as radical scavenging antioxidant activity. The compounds were assayed for their antiinflammatory activity in established in vivo models. The in vitro antioxidant activity was assessed in potassium ferricyanide reducing power (PFRAP) assay employing ascorbic acid as the standard drug. Results: Compounds (5, 6, 9 and 10) showed anti-inflammatory activity comparable to the standard drugs and were also found to be non-ulcerogenic at the test doses. Compounds 6-10 exhibited good antioxidant effect in the concentration range of 1.0-50.0 µmol/ml. The test compounds were also found to comply with the Lipinski rule suggesting good oral absorption. Conclusion: A new series of isoxazole based compounds is being reported with good anti-inflammatory activity coupled with antioxidant potential as gastro-sparing anti-inflammatory agents.

scholarly journals Autocrine IGF2 programmes β-cell plasticity under conditions of increased metabolic demand

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ionel Sandovici ◽  
Constanze M. Hammerle ◽  
Sam Virtue ◽  
Yurena Vivas-Garcia ◽  
Adriana Izquierdo-Lahuerta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Homeostasis ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Chow Diet ◽  
Genome Wide Association Studies ◽  
Cell Plasticity ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

AbstractWhen exposed to nutrient excess and insulin resistance, pancreatic β-cells undergo adaptive changes in order to maintain glucose homeostasis. The role that growth control genes, highly expressed in early pancreas development, might exert in programming β-cell plasticity in later life is a poorly studied area. The imprinted Igf2 (insulin-like growth factor 2) gene is highly transcribed during early life and has been identified in recent genome-wide association studies as a type 2 diabetes susceptibility gene in humans. Hence, here we investigate the long-term phenotypic metabolic consequences of conditional Igf2 deletion in pancreatic β-cells (Igf2βKO) in mice. We show that autocrine actions of IGF2 are not critical for β-cell development, or for the early post-natal wave of β-cell remodelling. Additionally, adult Igf2βKO mice maintain glucose homeostasis when fed a chow diet. However, pregnant Igf2βKO females become hyperglycemic and hyperinsulinemic, and their conceptuses exhibit hyperinsulinemia and placentomegalia. Insulin resistance induced by congenital leptin deficiency also renders Igf2βKO females more hyperglycaemic compared to leptin-deficient controls. Upon high-fat diet feeding, Igf2βKO females are less susceptible to develop insulin resistance. Based on these findings, we conclude that in female mice, autocrine actions of β-cell IGF2 during early development determine their adaptive capacity in adult life.

scholarly journals Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dopaminergic Neurons ◽  
Vagal Nerve ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

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