scholarly journals NFAT5 Is Involved in GRP-Enhanced Secretion of GLP-1 by Sodium

2021 ◽  
Vol 22 (8) ◽  
pp. 3951
Author(s):  
Caini Fan ◽  
Laureano D. Asico ◽  
Van Anthony M. Villar ◽  
Jessica Hunt ◽  
Santiago Cuevas ◽  
...  
Keyword(s):  
Sodium Concentration ◽  
Sodium Balance ◽  
High Sodium ◽  
L Cells ◽  
Sodium Hydrogen Exchanger ◽  
Enhanced Secretion ◽  
Glucagon Like Peptide 1 ◽  
New Perspective ◽  
Mouse Ileum

Gastrin, secreted by G-cells, and glucagon-like peptide-1 (GLP-1), secreted by L-cells, may participate in the regulation of sodium balance. We studied the effect of sodium in mice in vivo and mouse ileum and human L-cells, on GLP-1 secretion, and the role of NFAT5 and gastrin-releasing peptide receptor (GRPR) in this process. A high-sodium diet increases serum GLP-1 levels in mice. Increasing sodium concentration stimulates GLP-1 secretion from mouse ileum and L-cells. GRP enhances the high sodium-induced increase in GLP-1 secretion. High sodium increases cellular GLP-1 expression, while low and high sodium concentrations increase NFAT5 and GRPR expression. Silencing NFAT5 in L-cells abrogates the stimulatory effect of GRP on the high sodium-induced GLP-1 secretion and protein expression, and the sodium-induced increase in GRPR expression. GLP-1 and gastrin decrease the expression of Na+-K+/ATPase and increase the phosphorylation of sodium/hydrogen exchanger type 3 (NHE3) in human renal proximal tubule cells (hRPTCs). This study gives a new perspective on the mechanisms of GLP-1 secretion, especially that engendered by ingested sodium, and the ability of GLP-1, with gastrin, to decrease Na+-K+/ATPase expression and NHE3 function in hRPTCs. These results may contribute to the better utilization of current and future GLP-1-based drugs in the treatment of hypertension.

Chronic sodium loading augments natriuretic response to acute volume expansion in the preweaned rat

1995 ◽  
Vol 269 (1) ◽  
pp. R15-R22 ◽  
Author(s):  
D. G. Muchant ◽  
B. A. Thornhill ◽  
D. C. Belmonte ◽  
R. A. Felder ◽  
A. Baertschi ◽  
...  
Keyword(s):  
Volume Expansion ◽  
Sodium Intake ◽  
Somatic Growth ◽  
Sodium Concentration ◽  
Dietary Sodium ◽  
Sodium Balance ◽  
Urinary Flow ◽  
Adult Rats ◽  
High Sodium ◽  
Before And After

Positive sodium balance is necessary for normal somatic growth of the neonate, and the neonatal renal response to volume expansion (VE) is attenuated compared with the adult. To test the hypothesis that dietary sodium modulates the developmental response to VE, preweaned rats were artificially reared with either a normal (25 meq/l)- or high-sodium (145 meq/l) diet for 7-8 days and were compared with adult rats receiving normal or high sodium. Serum sodium concentration remained normal in adults on high sodium, whereas neonates became hypernatremic. Glomerular filtration rate (GFR), urinary flow (V), and urinary sodium (UNaV) were measured before and after acute saline VE (1% body wt). While remaining constant in preweaned rats, GFR increased > 50% in adult rats after VE (P < 0.05). High sodium intake augmented V and UNaV after VE but was not sustained in neonates as in adults. Plasma atrial natriuretic peptide (ANP) and guanosine 3',5'-cyclic monophosphate excretion (UcGMPV) were measured, and baseline UcGMPV was lower in preweaned rats receiving normal sodium but increased to levels similar to adult levels after VE. Postexpansion plasma ANP was higher in preweaned rats than in adult rats and was not affected by dietary sodium regardless of age. We conclude that the attenuated postexpansion natriuresis in the neonate is due in part to an adaptive response to limited sodium intake. However, neonatal compensation to increased sodium intake is incomplete and independent of plasma ANP.

scholarly journals Liraglutide Suppresses the Plasma Levels of Active and Des-Acyl Ghrelin Independently of Active Glucagon-Like Peptide-1 Levels in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Katsunori Nonogaki ◽  
Marina Suzuki
Keyword(s):  
Plasma Levels ◽  
Biological Effect ◽  
Systemic Administration ◽  
Elevated Plasma ◽  
L Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Acyl Ghrelin

Glucagon-like peptide-1 (GLP-1), an insulinotropic gastrointestinal peptide that is primarily produced by intestinal endocrine L-cells, stimulates satiety. Ghrelin, a hormone that is produced predominantly by the stomach stimulates hunger. There are two forms of ghrelin: active ghrelin and inactive des-acyl ghrelin. After depriving mice of food for 24 h, we demonstrated that the systemic administration of liraglutide (100 μg/kg), a human GLP-1 analog that binds to the GLP-1 receptor, increased (1.4-fold) the plasma levels of active GLP-1 and suppressed the plasma levels of active and des-acyl ghrelin after 1 h. Despite the elevated plasma levels of active GLP-1 (11-fold), liraglutide had no effect on the plasma levels of active or des-acyl ghrelin after 12 h. These findings demonstrated that liraglutide suppresses the plasma levels of active and des-acyl ghrelin independently of active GLP-1 levels in fasted mice, suggesting a novel in vivo biological effect of liraglutide beyond regulating plasma GLP-1.

scholarly journals GLP-1 localisation and proglucagon gene expression in healthy and diabetic mouse ileum

2018 ◽  
Vol 62 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Serap Koral Taşçı ◽  
Seyit Ali Bingöl
Keyword(s):  
Gene Expression ◽  
Diabetic Mouse ◽  
Control Groups ◽  
L Cells ◽  
Polymerase Chain ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
And Control ◽  
Gene Expression Levels ◽  
Mouse Ileum

AbstractIntroductionGlucagon-like peptide-1 (GLP-1) is a polypeptide that is mainly produced by intestinal L cells and is encoded by the proglucagon gene. In this study, GLP-1 localisation was investigated in the ileum of healthy and diabetic mice by immunohistochemistry and proglucagon gene expression was assayed by reverse transcription-polymerase chain reaction.Material and MethodsThis study included 18 male Balb/c mice that were divided into diabetic, sham, and control groups. Mice in the diabetic group received 100 mg/kg of streptozotocin. Immunohistochemical expression of GLP-1 was determined using the avidin–biotin–peroxidase complex technique, and proglucagon gene expression was determined by RT-PCR.ResultsAnalysis of GLP-1 immunohistochemical localisation showed that GLP-1-immunopositive cells (L cells) were present between epithelial cells in the intestinal crypts. The intensity and localisation of GLP-1 immunoreactivity were similar among the mice in all the groups. Proglucagon gene expression levels were also statistically similar among the mice in all the groups.ConclusionNo difference was demonstrated among the mice in the diabetic, sham, or control groups with respect to proglucagon gene expression and GLP-1 localisation in the ileum, suggesting that diabetes does not affect proglucagon gene expression in the ileum.

scholarly journals The Melanocortin-4 Receptor Is Expressed in Enteroendocrine L Cells and Regulates the Release of Peptide YY and Glucagon-like Peptide 1 In Vivo

2014 ◽  
Vol 20 (6) ◽  
pp. 1018-1029 ◽  
Author(s):  
Brandon L. Panaro ◽  
Iain R. Tough ◽  
Maja S. Engelstoft ◽  
Robert T. Matthews ◽  
Gregory J. Digby ◽  
...  
Keyword(s):  
Peptide Yy ◽  
L Cells ◽  
Melanocortin 4 Receptor ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Tinospora cordifolia Aqueous Extract Alleviates Cyclophosphamide- Induced Immune Suppression, Toxicity and Systemic Candidiasis in Immunosuppressed Mice: In vivo Study in Comparison to Antifungal Drug Fluconazole

2019 ◽  
Vol 20 (12) ◽  
pp. 1055-1063 ◽  
Author(s):  
Faris Alrumaihi ◽  
Khaled S. Allemailem ◽  
Ahmad Almatroudi ◽  
Mohammed A. Alsahli ◽  
Arif Khan ◽  
...  
Keyword(s):  
Survival Rate ◽  
Aqueous Extract ◽  
Survival Data ◽  
Tinospora Cordifolia ◽  
Systemic Candidiasis ◽  
Organ Index ◽  
Tnf Α ◽  
Fungal Load ◽  
Enhanced Secretion

Objective: The present study was aimed to evaluate the effect of the aqueous extract of Tinospora cordifolia (AETC) against cyclophosphamide-induced immunosuppression and systemic Candida albicans infection in a murine model. Methods: The protective effect of AETC against cyclophosphamide-induced leukopenia was evaluated by quantitative and qualitative analysis of the leukocytes. The immune-stimulating potential of AETC on macrophages was assessed by determining the levels of secreted cytokines. To determine the direct antifungal activity, AETC or fluconazole was administered to C. albicans infected mice. The efficacy of treatment was assessed by determining the survival rate, kidney fungal burden, the organ index and liver inflammation parameters. Results: Cyclophosphamide administration resulted in substantial depletion of leukocytes, whereas AETC treatment induced the recovery of leukocytes in cyclophosphamide-injected mice. Moreover, AETC treatment of macrophages resulted in enhanced secretion of IFN-γ, TNF-α and IL-1β. C. albicans infected mice treated with AETC at the doses of 50 and 100 mg/kg exhibited 40% and 60% survival rate, whereas the mice treated with fluconazole at a dose of 50 mg/kg showed 20% survival rate. Like survival data, the fungal load was found to be the lowest in the kidney tissues of mice treated with AETC at a dose of 100 mg/kg. Interestingly, mice infected with C. albicans demonstrated improvement in the organ indices and liver functioning after AETC treatment. Conclusion: These results suggest that AETC may potentially be used to rejuvenate the weakened immune system and eliminate systemic candidiasis in mice.

Let-7e-5p Regulates GLP-1 Content and Basal Release From Enteroendocrine L Cells From DIO Male Mice

Endocrinology ◽  
2019 ◽  
Vol 161 (2) ◽  
Author(s):  
Sandra Handgraaf ◽  
Rodolphe Dusaulcy ◽  
Florian Visentin ◽  
Jacques Philippe ◽  
Yvan Gosmain
Keyword(s):  
Compensatory Mechanism ◽  
L Cells ◽  
Low Fat Diet ◽  
Obesity And Diabetes ◽  
Basal Release ◽  
Glucagon Like Peptide 1 ◽  
Cell Transcriptome ◽  
Microarray Analyses

Abstract Characterization of enteroendocrine L cells in diabetes is critical for better understanding of the role of glucagon-like peptide-1 (GLP-1) in physiology and diabetes. We studied L-cell transcriptome changes including microRNA (miRNA) dysregulation in obesity and diabetes. We evaluated the regulation of miRNAs through microarray analyses on sorted enteroendocrine L cells from control and obese glucose-intolerant (I-HFD) and hyperglycemic (H-HFD) mice after 16 weeks of respectively low-fat diet (LFD) or high-fat diet (HFD) feeding. The identified altered miRNAs were studied in vitro using the mouse GLUTag cell line to investigate their regulation and potential biological functions. We identified that let-7e-5p, miR-126a-3p, and miR-125a-5p were differentially regulated in L cells of obese HFD mice compared with control LFD mice. While downregulation of let-7e-5p expression was observed in both I-HFD and H-HFD mice, levels of miR-126a-3p increased and of miR-125a-5p decreased significantly only in I-HFD mice compared with controls. Using miRNA inhibitors and mimics we observed that modulation of let-7e-5p expression affected specifically GLP-1 cellular content and basal release, whereas Gcg gene expression and acute GLP-1 secretion and cell proliferation were not affected. In addition, palmitate treatment resulted in a decrease of let-7e-5p expression along with an increase in GLP-1 content and release, suggesting that palmitate acts on GLP-1 through let-7e-5p. By contrast, modulation of miR-125a-5p and miR-126a-3p in the same conditions did not affect content or secretion of GLP-1. We conclude that decrease of let-7e-5p expression in response to palmitate may constitute a compensatory mechanism contributing to maintaining constant glycemia in obese mice.

scholarly journals Glucolipotoxicity and GLP-1 secretion

2021 ◽  
Vol 9 (1) ◽  
pp. e001905
Author(s):  
Jung-Hee Hong ◽  
Dae-Hee Kim ◽  
Moon-Kyu Lee
Keyword(s):  
Glucose Transporter ◽  
Cell Function ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Gene Expressions ◽  
Simultaneous Treatment ◽  
L Cells ◽  
Triglyceride Accumulation

IntroductionThe concept of glucolipotoxicity refers to the combined, deleterious effects of elevated glucose and/or fatty acid levels.Research design and methodsTo investigate the effects of chronic glucolipotoxicity on glucagon-like peptide-1-(7-36) amide (GLP-1) secretion, we generated glucolipotoxic conditions in human NCI-H716 enteroendocrine cells using either 5 or 25 mM glucose with or without 500 µM palmitate for 72 hours. For in vivo study, we have established a chronic nutrient infusion model in the rat. Serial blood samples were collected for 2 hours after the consumption of a mixed meal to evaluate insulin sensitivity and β-cell function.ResultsChronic glucolipotoxic conditions decreased GLP-1 secretion and the expressions of pCREB, pGSK3β, β-catenin, and TCF7L2 in NCI-H716 cells. Glucolipotoxicity conditions reduced glucose transporter expression, glucose uptake, and nicotinamide-adenine dinucleotide phosphate (NADPH) levels in L-cells, and increased triglyceride accumulation. In contrast, PPARα and ATP levels were reduced, which correlated well with decreased levels of SUR1 and Kir6.2, cAMP contents and expressions of pCAMK2, EPAC and PKA. We also observed an increase in reactive oxygen species production, UCP2 expression and Complex I activity. Simultaneous treatment with insulin restored the GLP-1 secretion. Glucolipotoxic conditions decreased insulin secretion in a time-dependent manner in INS-1 cells, which was recovered with exendin-4 cotreatment. Glucose and SMOFlipid infusion for 6 hours decreased GLP-1 secretion and proglucagon mRNA levels as well as impaired the glucose tolerance, insulin and C-peptide secretion in rats.ConclusionThese results provide evidence for the first time that glucolipotoxicity could affect GLP-1 secretion through changes in glucose and lipid metabolism, gene expressions, and proglucagon biosynthesis and suggest the interrelationship between glucolipotoxicities of L-cells and β-cells which develops earlier than that of L-cells.

scholarly journals Sodium Radiofrequency Coils for Magnetic Resonance: From Design to Applications

Electronics ◽  
2021 ◽  
Vol 10 (15) ◽  
pp. 1788
Author(s):  
Giulio Giovannetti ◽  
Alessandra Flori ◽  
Nicola Martini ◽  
Roberto Francischello ◽  
Giovanni Donato Aquaro ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Sodium Concentration ◽  
Resonance Spectroscopy ◽  
Sodium Mri ◽  
Human Organs ◽  
Low Sodium ◽  
Radiofrequency Coils ◽  
Anatomical Imaging ◽  
Strong Gradient

Sodium (23Na) is the most abundant cation present in the human body and is involved in a large number of vital body functions. In the last few years, the interest in Sodium Magnetic Resonance Imaging (23Na MRI) has considerably increased for its relevance in physiological and physiopathological aspects. Indeed, sodium MRI offers the possibility to extend the anatomical imaging information by providing additional and complementary information on physiology and cellular metabolism with the heteronuclear Magnetic Resonance Spectroscopy (MRS). Constraints are the rapidly decaying of sodium signal, the sensitivity lack due to the low sodium concentration versus 1H-MRI induce scan times not clinically acceptable and it also constitutes a challenge for sodium MRI. With the available magnetic fields for clinical MRI scanners (1.5 T, 3 T, 7 T), and the hardware capabilities such as strong gradient strengths with high slew rates and new dedicated radiofrequency (RF) sodium coils, it is possible to reach reasonable measurement times (~10–15 min) with a resolution of a few millimeters, where it has already been applied in vivo in many human organs such as the brain, cartilage, kidneys, heart, as well as in muscle and the breast. In this work, we review the different geometries and setup of sodium coils described in the available literature for different in vivo applications in human organs with clinical MR scanners, by providing details of the design, modeling and construction of the coils.

scholarly journals Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents

2019 ◽  
Vol 316 (5) ◽  
pp. G574-G584 ◽  
Author(s):  
Charlotte Bayer Christiansen ◽  
Samuel Addison Jack Trammell ◽  
Nicolai Jacob Wewer Albrechtsen ◽  
Kristina Schoonjans ◽  
Reidar Albrechtsen ◽  
...  
Keyword(s):  
Bile Acids ◽  
G Protein ◽  
Peptide Yy ◽  
Whole Body ◽  
Rat Colon ◽  
G Protein Coupled Receptor ◽  
L Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion.NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.

scholarly journals Unraveling the neurotoxicity of titanium dioxide nanoparticles: focusing on molecular mechanisms

2016 ◽  
Vol 7 ◽  
pp. 645-654 ◽  
Author(s):  
Bin Song ◽  
Yanli Zhang ◽  
Jia Liu ◽  
Xiaoli Feng ◽  
Ting Zhou ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Titanium Dioxide ◽  
Molecular Mechanisms ◽  
Titanium Dioxide Nanoparticles ◽  
Brain Dysfunction ◽  
In Vivo Studies ◽  
Cell Components ◽  
New Perspective ◽  
The Brain

Titanium dioxide nanoparticles (TiO2 NPs) possess unique characteristics and are widely used in many fields. Numerous in vivo studies, exposing experimental animals to these NPs through systematic administration, have suggested that TiO2 NPs can accumulate in the brain and induce brain dysfunction. Nevertheless, the exact mechanisms underlying the neurotoxicity of TiO2 NPs remain unclear. However, we have concluded from previous studies that these mechanisms mainly consist of oxidative stress (OS), apoptosis, inflammatory response, genotoxicity, and direct impairment of cell components. Meanwhile, other factors such as disturbed distributions of trace elements, disrupted signaling pathways, dysregulated neurotransmitters and synaptic plasticity have also been shown to contribute to neurotoxicity of TiO2 NPs. Recently, studies on autophagy and DNA methylation have shed some light on possible mechanisms of nanotoxicity. Therefore, we offer a new perspective that autophagy and DNA methylation could contribute to neurotoxicity of TiO2 NPs. Undoubtedly, more studies are needed to test this idea in the future. In short, to fully understand the health threats posed by TiO2 NPs and to improve the bio-safety of TiO2 NPs-based products, the neurotoxicity of TiO2 NPs must be investigated comprehensively through studying every possible molecular mechanism.

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