Role of nitric oxide in the regulation of glucose kinetics in response to endotoxin in dogs

2001 ◽  
Vol 91 (1) ◽  
pp. 130-136 ◽  
Author(s):  
H. S. Moeniralam ◽  
F. Sprangers ◽  
E. Endert ◽  
M. T. Ackermans ◽  
J. J. B. Van Lanschot ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Lactate ◽  
E Coli ◽  
Glucose Levels ◽  
High Doses ◽  
Glucose Plasma

The purpose of the present in vivo study was to determine the role of nitric oxide (NO) in the regulation of glucose metabolism in response to endotoxin by blocking NO synthesis with NG-monomethyl-l-arginine (l-NMMA). In five dogs, the appearance and disappearance rates of glucose (by infusion of [6,6-2H2]glucose), plasma glucose concentration, and plasma hormone concentrations were measured on five different occasions: saline infusion, endotoxin alone ( E coli, 1.0 μg/kg iv), and endotoxin administration plus three different doses of primed, continuous infusion of l-NMMA. Endotoxin increased rate of appearance of glucose from 13.7 ± 1.6 to 23.6 ± 3.3 μmol · kg−1· min−1( P < 0.05), rate of disappearance of glucose from 13.9 ± 1.1 to 24.8 ± 3.1 μmol · kg−1· min−1( P < 0.001), plasma lactate from 0.5 ± 0.1 to 1.7 ± 0.1 mmol/l ( P < 0.01), and counterregulatory hormone concentrations. l-NMMA did not affect the rise in rate of appearance and disappearance of glucose, plasma lactate, or the counterregulatory hormone response to endoxin. Plasma glucose levels were not affected by endotoxin with or withoutl-NMMA. In conclusion, in vivo inhibition of NO synthesis by high doses of l-NMMA does not affect glucose metabolism in response to endotoxin, indicating that NO is not a major mediator of glucose metabolism during endotoxemia in dogs.

scholarly journals Examination of Potential Mechanisms in the Enhancement of Cerebral Blood Flow by Hypoglycemia and Pharmacological Doses of Deoxyglucose

1997 ◽  
Vol 17 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Naoaki Horinaka ◽  
Nicole Artz ◽  
Jane Jehle ◽  
Shinichi Takahashi ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Lactate ◽  
Insulin Hypoglycemia ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Arterial Plasma

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 m M, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3– concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 m M) or pharmacological doses of deoxyglucose.

Abstract 3512: Disruption of Whole Nitric Oxide Synthase System Causes Impaired Glucose Tolerance and Insulin Resistance in Mice in Vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sei Nakata ◽  
Masato Tsutsui ◽  
Hiroaki Shimokawa ◽  
Ken Sabanai ◽  
Yasuko Yatera ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Pancreatic Islets ◽  
Plasma Glucose ◽  
Insulin Levels

Background : Nitric oxide (NO) synthase (NOS) system consists of 3 different isoforms, including neuronal (nNOS), inducible (iNOS), and endothelial NOSs (eNOS). We have recently succeeded in developing mice lacking all NOS genes (triply n/i/eNOS-KO mice) ( PNAS 2005). Our preliminary study has revealed that the triply-KO mice develop acute myocardial infarction (AMI). The present study was designed to investigate abnormalities of glucose metabolism, an important risk factor of MI, in those mice. Methods and Results : Experiments were performed in 3-month-old male wild-type (WT) and triply-KO mice (n=5–7). At 15 minutes after intravenous glucose administration (1 g/kg), plasma glucose levels (mg/dl) were significantly higher in the triply-KO (475 ± 44) than in the WT mice (241 ± 20) ( P< 0.05), and plasma insulin levels (ng/dl) were significantly lower in the triply-KO (0.50 ± 0.03) than in the WT mice (0.78 ± 0.03) ( P< 0.05). In the triply-KO mice, the size of pancreatic islets (islet/pancreatic area, 0.64 ± 0.16 vs. 2.81 ± 0.64%) was significantly smaller ( P< 0.05), and significant apoptosis of pancreatic islets (apoptotic/total islets, 19 ± 2 vs. 3 ± 1%) (TUNEL staining) was noted as compared with the WT mice ( P< 0.05). Furthermore, insulin sensitivity (as assessed by insulin-induced [ 3 H]-glucose uptake in isolated soleus muscle) (fold increase) was markedly reduced in the triply-KO mice (1.1 ± 0.03) as compared with the WT mice (2.1 ± 0.3) ( P< 0.05), associated with an impairment of insulin-induced translocation of glucose transporter-4 (GLUT-4) to the cellular membrane (immunofluorescent staining) ( P< 0.05). Importantly, supplementation of NO by long-term treatment with isosorbide dinitrate (0.4 mg/day, 6 weeks, dermal application) significantly reversed all these abnormalities of glucose metabolism in the triply-KO mice; plasma glucose (280 ± 28) and insulin levels (0.89 ± 0.10) after glucose tolerance test, insulin sensitivity (1.5 ± 0.08), and GLUT-4 translocation were all improved (all P< 0.05). Conclusions : These results indicate that disruption of whole NOSs system causes impaired glucose tolerance and insulin resistance in mice in vivo, suggesting a critical role of endogenous NO/NOSs system in maintaining glucose metabolism.

scholarly journals Role of Glucose in IRS Signaling in Rat Pancreatic Islets: Specific Effects and Interplay with Insulin

2004 ◽  
Vol 5 (4) ◽  
pp. 257-263 ◽  
Author(s):  
Maryline Paris ◽  
Catherine Bernard-Kargar ◽  
José Vilar ◽  
Nadim Kassis ◽  
Alain Ktorza
Keyword(s):  
Mrna Expression ◽  
Plasma Glucose ◽  
Secretory Process ◽  
Special Focus ◽  
Glucose Signaling ◽  
Glucose Levels ◽  
Complementary Role ◽  
And Function

We investigated the possible interplay between insulin and glucose signaling pathways in rat pancreaticβ-cell with a special focus on the role of glucose in IRS signalingin vivo. Three groups of rats were constituted by combining simultaneous infusion during 48 h either of glucose and/or insulin, or glucose+diazoxide: Hyperglycemic- Hyperinsulinemic (HGHI), euglycemic-Hyperinsulinemic (eGHI), Hyperglycemic-euinsulinemic (HGeI). Control rats were infused with 0,9% NaCl. In HGHI and HGeI rats plasma glucose levels were maintained at 20-22 mmol/l. In eGHI rats, plasma glucose was not different from that of controls, whereas plasma insulin was much higher than in controls. In HGHI rats, IRS-2 mRNA expression, total protein and phosphorylated protein amounts were increased compared to controls. In HGeI rats, only IRS-2 mRNA expression was increased. No change was observed in eGHI rats whatever the parameter considered. In all groups, mRNA concentration of IRS-1 was similar to that of controls. The quantity of total and phosphorylated IRS- 1 protein was dramatically increased in HGHI rats and to a lesser extent in eGHI rats. Neither mRNA nor IRS-1 protein expression were modified in HGeI rats. The data suggest that glucose and insulin play at once a specific and a complementary role in islet IRSs signaling. Especially, glucose stimulates IRS-2 mRNA expression whatever the insulin status and independently of the secretory process. The differential regulation of IRS-1 and IRS-2 expressions is in agreement with their supposed different involvement in the control ofβ-cell growth and function.

Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1β in Pigs in Vivo

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Chronic Treatment ◽  
Interleukin 1Β ◽  
Coronary Lesions ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Arabidopsis Disulfide Reductase, Trx-h2, Functions as an RNA Chaperone under Cold Stress

2021 ◽  
Vol 11 (15) ◽  
pp. 6865
Author(s):  
Eun Seon Lee ◽  
Joung Hun Park ◽  
Seong Dong Wi ◽  
Ho Byoung Chae ◽  
Seol Ki Paeng ◽  
...  
Keyword(s):  
Cold Stress ◽  
Wild Type ◽  
Rna Chaperone ◽  
E Coli ◽  
Cold Sensitive ◽  
Thioredoxin H ◽  
Functional Rnas

The thioredoxin-h (Trx-h) family of Arabidopsis thaliana comprises cytosolic disulfide reductases. However, the physiological function of Trx-h2, which contains an additional 19 amino acids at its N-terminus, remains unclear. In this study, we investigated the molecular function of Trx-h2 both in vitro and in vivo and found that Arabidopsis Trx-h2 overexpression (Trx-h2OE) lines showed significantly longer roots than wild-type plants under cold stress. Therefore, we further investigated the role of Trx-h2 under cold stress. Our results revealed that Trx-h2 functions as an RNA chaperone by melting misfolded and non-functional RNAs, and by facilitating their correct folding into active forms with native conformation. We showed that Trx-h2 binds to and efficiently melts nucleic acids (ssDNA, dsDNA, and RNA), and facilitates the export of mRNAs from the nucleus to the cytoplasm under cold stress. Moreover, overexpression of Trx-h2 increased the survival rate of the cold-sensitive E. coli BX04 cells under low temperature. Thus, our data show that Trx-h2 performs function as an RNA chaperone under cold stress, thus increasing plant cold tolerance.

scholarly journals Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 420
Author(s):  
Su-Jung Hwang ◽  
Ye-Seul Song ◽  
Hyo-Jong Lee
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Network Pharmacology ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Bioactive Constituents

Kushen (Radix Sophorae flavescentis) is used to treat ulcerative colitis, tumors, and pruritus. Recently, phaseolin, formononetin, matrine, luteolin, and quercetin, through a network pharmacology approach, were tentatively identified as five bioactive constituents responsible for the anti-inflammatory effects of S. flavescentis. However, the role of phaseolin (one of the primary components of S. flavescentis) in the direct regulation of inflammation and inflammatory processes is not well known. In this study, the beneficial role of phaseolin against inflammation was explored in lipopolysaccharide (LPS)-induced inflammation models of RAW 264.7 macrophages and zebrafish larvae. Phaseolin inhibited LPS-mediated production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), without affecting cell viability. In addition, phaseolin suppressed pro-inflammatory mediators such as cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in a dose-dependent manner. Furthermore, phaseolin reduced matrix metalloproteinase (MMP) activity as well as macrophage adhesion in vitro and the recruitment of leukocytes in vivo by downregulating Ninjurin 1 (Ninj1), an adhesion molecule. Finally, phaseolin inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB). In view of the above, our results suggest that phaseolin could be a potential therapeutic candidate for the management of inflammation.

scholarly journals Novel Insights on the Role of Nitric Oxide in the Ovary: A Review of the Literature

2021 ◽  
Vol 18 (3) ◽  
pp. 980
Author(s):  
Maria Cristina Budani ◽  
Gian Mario Tiboni
Keyword(s):  
Nitric Oxide ◽  
In Vivo Studies ◽  
Published Data ◽  
Vitro Fertilization ◽  
Peripheral Neurons ◽  
Relevant Role ◽  
Oocyte Meiotic Maturation

Nitric oxide (NO) is formed during the oxidation of L-arginine to L-citrulline by the action of multiple isoenzymes of NO synthase (NOS): neuronal NOS (nNOS), endotelial NOS (eNOS), and inducible NOS (iNOS). NO plays a relevant role in the vascular endothelium, in central and peripheral neurons, and in immunity and inflammatory systems. In addition, several authors showed a consistent contribution of NO to different aspects of the reproductive physiology. The aim of the present review is to analyse the published data on the role of NO within the ovary. It has been demonstrated that the multiple isoenzymes of NOS are expressed and localized in the ovary of different species. More to the point, a consistent role was ascribed to NO in the processes of steroidogenesis, folliculogenesis, and oocyte meiotic maturation in in vitro and in vivo studies using animal models. Unfortunately, there are few nitric oxide data for humans; there are preliminary data on the implication of nitric oxide for oocyte/embryo quality and in-vitro fertilization/embryo transfer (IVF/ET) parameters. NO plays a remarkable role in the ovary, but more investigation is needed, in particular in the context of human ovarian physiology.

scholarly journals A Role for Fas in Negative Selection of Thymocytes In Vivo

1998 ◽  
Vol 187 (9) ◽  
pp. 1427-1438 ◽  
Author(s):  
Hidehiro Kishimoto ◽  
Charles D. Surh ◽  
Jonathan Sprent
Keyword(s):  
Negative Selection ◽  
Cell Receptor ◽  
Staphylococcal Enterotoxin B ◽  
Thymic Medulla ◽  
Enterotoxin B ◽  
High Doses ◽  
Specific Peptide ◽  
Selection Of

To seek information on the role of Fas in negative selection, we examined subsets of thymocytes from normal neonatal mice versus Fas-deficient lpr/lpr mice injected with graded doses of antigen. In normal mice, injection of 1–100 μg of staphylococcal enterotoxin B (SEB) induced clonal elimination of SEB-reactive Vβ8+ cells at the level of the semi-mature population of HSAhi CD4+ 8− cells found in the thymic medulla; deletion of CD4+ 8+ cells was minimal. SEB injection also caused marked elimination of Vβ8+ HSAhi CD4+ 8− thymocytes in lpr/lpr mice. Paradoxically, however, elimination of these cells in lpr/lpr mice was induced by low-to-moderate doses of SEB (≤1 μg) but not by high doses (100 μg). Similar findings applied when T cell receptor transgenic mice were injected with specific peptide. These findings suggest that clonal elimination of semi-mature medullary T cells is Fas independent at low doses of antigen but Fas dependent at high doses. Previous reports documenting that negative selection is not obviously impaired in lpr/lpr mice could thus reflect that the antigens studied were expressed at only a low level.

Insulin and glucagon in rats with Islet cell tumors Induced by small doses of streptozofoclii

1981 ◽  
Vol 59 (8) ◽  
pp. 818-823 ◽  
Author(s):  
Gen Yoshino ◽  
Tsutomu Kazumi ◽  
Soichiro Morita ◽  
Shighaki Baba
Keyword(s):  
Plasma Glucose ◽  
Islet Cell ◽  
Insulin Response ◽  
Oral Glucose ◽  
Islet Cell Tumors ◽  
Glucose Levels ◽  
Tumor Bearing ◽  
Small Doses ◽  
Wet Weight ◽  
Glucose Plasma

Plasma insulin and glucagon responses to oral glucose loading were examined in rats with islet cell tumors induced by a single intravenous injection of streptozotocin (30 or 40 mg/kg body weight). Twenty-four macroscopic and six microscopic tumors occurred in 21 rats. In 15 of 21 tumor-bearing rats, there was exaggerated insulin release in response to oral glucose. Plasma glucose levels did not rise with the oral glucose load and were comparable to those seen in normal animals. Hence these rats are described as having "responsive tumors." In six rats with "nonresponsive tumors" there was no insulin response and the plasma glucose levels rose. No significant differences in plasma glucagon levels were observed between the two groups. Nonresponsive tumors as well as responsive tumors contained a significant amount of extractable insulin (17.68 ± 8.60 and 35.07 ± 10.05 mg/g wet weight, respectively) and detectable amounts of immunoreactive glucagon (1.47 ± 0.61 and 2.24 ± 0.67 μg/g wet weight, respectively).These results suggest that a small dose of streptozotocin produces two types of islet cell tumors. One is insulin producing and insulin secreting whereas the other is insulin producing but not insulin secreting.

DNA methylation in Yersinia enterocolitica: role of the DNA adenine methyltransferase in mismatch repair and regulation of virulence factors

Microbiology ◽  
2005 ◽  
Vol 151 (7) ◽  
pp. 2291-2299 ◽  
Author(s):  
Stefan Fälker ◽  
M. Alexander Schmidt ◽  
Gerhard Heusipp
Keyword(s):  
Mismatch Repair ◽  
Yersinia Enterocolitica ◽  
Virulence Genes ◽  
Spontaneous Mutation ◽  
Gram Negative Bacteria ◽  
E Coli ◽  
Physiological Processes ◽  
Dna Adenine Methyltransferase

DNA adenine methyltransferase (Dam) plays an important role in physiological processes of Gram-negative bacteria such as mismatch repair and replication. In addition, Dam regulates the expression of virulence genes in various species. The authors cloned the dam gene of Yersinia enterocolitica and showed that Dam is essential for viability. Dam overproduction in Y. enterocolitica resulted in an increased frequency of spontaneous mutation and decreased resistance to 2-aminopurine; however, these effects were only marginal compared to the effect of overproduction of Escherichia coli-derived Dam in Y. enterocolitica, implying different roles or activities of Dam in mismatch repair of the two species. These differences in Dam function are not the cause for the essentiality of Dam in Y. enterocolitica, as Dam of E. coli can complement a dam defect in Y. enterocolitica. Instead, Dam seems to interfere with expression of essential genes. Furthermore, Dam mediates virulence of Y. enterocolitica. Dam overproduction results in increased tissue culture invasion of Y. enterocolitica, while the expression of specifically in vivo-expressed genes is not altered.

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