scholarly journals Influence of C-Peptide on Glucose Utilisation

2008 ◽  
Vol 2008 ◽  
pp. 1-3 ◽  
Author(s):  
B. Wilhelm ◽  
P. Kann ◽  
A. Pfützner
Keyword(s):  
Nitric Oxide ◽  
Glucose Metabolism ◽  
No Synthase ◽  
In Vitro Studies ◽  
Glomerular Hyperfiltration ◽  
Physiological Effects ◽  
C Peptide ◽  
Glucose Utilisation ◽  
Endothelial Nitric Oxide

During the recent years, multiple studies demonstrated that C-peptide is not an inert peptide, but exerts important physiological effects. C-peptide binds to cell membranes, stimulates the Na,K-ATPase and the endothelial nitric oxide (NO) synthase. Moreover, there is evidence that C-peptide decreases glomerular hyperfiltration and increases glucose utilisation. Nevertheless, there is still limited knowledge concerning mechanisms leading to an increased glucose utilisation either in rats or in humans. The aim of this paper is to give an overview over the published studies regarding C-peptide and glucose metabolism from in vitro studies to longer lasting studies in humans.

Calcium regulates estrogen increase in permeability of cultured CaSki epithelium by eNOS-dependent mechanism

2000 ◽  
Vol 279 (5) ◽  
pp. C1495-C1505 ◽  
Author(s):  
George I. Gorodeski
Keyword(s):  
Nitric Oxide ◽  
Endothelial Nitric Oxide Synthase ◽  
Cytosolic Calcium ◽  
No Synthase ◽  
Calcium Dependent ◽  
Steady State Levels ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Dependent Mechanism

Estrogen increases baseline transepithelial permeability across CaSki cultures and augments the increase in permeability in response to hypertonic gradients. In estrogen-treated cells, lowering cytosolic calcium abrogated the hypertonicity-induced augmented increase in permeability and decreased baseline permeability to a greater degree than in estrogen-deprived cells. Steady-state levels of cytosolic calcium in estrogen-deprived cells were higher than in estrogen-treated cells. Increases in extracellular calcium increased cytosolic calcium more in estrogen-deprived cells than in estrogen-treated cells. However, in estrogen-treated cells, increasing cytosolic calcium was associated with greater increases in permeability in response to hypertonic gradients than in estrogen-deprived cells. Lowering cytosolic calcium blocked the estrogen-induced increase in nitric oxide (NO) release and in the in vitro conversion of l-[3H]arginine to l-[3H]citrulline. Treatment with estrogen upregulated mRNA of the NO synthase isoform endothelial nitric oxide synthase (eNOS). These results indicate that cytosolic calcium mediates the responses to estrogen and suggest that the estrogen increase in permeability and the augmented increase in permeability in response to hypertonicity involve an increase in NO synthesis by upregulation of the calcium-dependent eNOS.

scholarly journals Acetylcholine causes endothelium-dependent contraction of mouse arteries

2005 ◽  
Vol 289 (3) ◽  
pp. H1027-H1032 ◽  
Author(s):  
Yingbi Zhou ◽  
Saradhadevi Varadharaj ◽  
Xue Zhao ◽  
Narasimham Parinandi ◽  
Nicholas A. Flavahan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Isometric Tension ◽  
No Synthase ◽  
Cyclooxygenase Inhibitor ◽  
Wild Type ◽  
Endothelial Denudation ◽  
Prostaglandin H ◽  
Endothelial Nitric Oxide ◽  
Endothelium Dependent Relaxation

The goal of this study was to determine whether acetylcholine evokes endothelium-dependent contraction in mouse arteries and to define the mechanisms involved in regulating this response. Arterial rings isolated from wild-type (WT) and endothelial nitric oxide (NO) synthase knockout (eNOS−/−) mice were suspended for isometric tension recording. In abdominal aorta from WT mice contracted with phenylephrine, acetylcholine caused a relaxation that reversed at the concentration of 0.3–3 μM. After inhibition of NO synthase [with Nω-nitro-l-arginine methyl ester (l-NAME), 1 mM], acetylcholine (0.1–10 μM) caused contraction under basal conditions or during constriction to phenylephrine, which was abolished by endothelial denudation. This contraction was inhibited by the cyclooxygenase inhibitor indomethacin (1 μM) or by a thromboxane A2 (TxA2) and/or prostaglandin H2 receptor antagonist SQ-29548 (1 μM) and was associated with endothelium-dependent generation of the TxA2 metabolite TxB2. Also, SQ-29548 (1 μM) abolished the reversal in relaxation evoked by 0.3–3 μM acetylcholine and subsequently enhanced the relaxation to the agonist. The magnitude of the endothelium-dependent contraction to acetylcholine (0.1–10 μM) was similar in aortas from WT mice treated in vitro with l-NAME and from eNOS−/− mice. In addition, we found that acetylcholine (10 μM) also caused endothelium-dependent contraction in carotid and femoral arteries of eNOS−/− mice. These results suggest that acetylcholine initiates two competing responses in mouse arteries: endothelium-dependent relaxation mediated predominantly by NO and endothelium-dependent contraction mediated most likely by TxA2.

scholarly journals New nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold: Design, synthesis, in silico and in vitro studies

2021 ◽  
Vol 139 ◽  
pp. 111678
Author(s):  
Alexandru Sava ◽  
Frederic Buron ◽  
Sylvain Routier ◽  
Alina Panainte ◽  
Nela Bibire ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
In Silico ◽  
In Vitro Studies ◽  
Scaffold Design ◽  
Design Synthesis ◽  
Nitric Oxide Releasing

Pulmonary endothelial nitric oxide production is developmentally regulated in the fetus and newborn

1993 ◽  
Vol 265 (4) ◽  
pp. H1056-H1063 ◽  
Author(s):  
P. W. Shaul ◽  
M. A. Farrar ◽  
R. R. Magness
Keyword(s):  
Nitric Oxide ◽  
Vascular Resistance ◽  
Pulmonary Arteries ◽  
Late Gestation ◽  
No Production ◽  
Third Trimester ◽  
Developmentally Regulated ◽  
The Third ◽  
Endothelial Nitric Oxide

To define the role of endothelial nitric oxide (NO) in developmental changes in pulmonary vascular resistance and oxygen responsiveness, we determined the ontogeny of endothelial NO production and of oxygen modulation of that process in pulmonary arteries from fetal and newborn lambs. NO production was assessed by measuring endothelium-dependent arterial guanosine 3',5'-cyclic monophosphate synthesis. Basal NO rose two-fold from late gestation to 1 wk of age and another 1.6-fold from 1 to 4 wk. Acetylcholine-stimulated NO also increased 1.6-fold from 1 to 4 wk. The maturational rise in NO was evident at high Po2 in vitro, and it was not modified by L-arginine. This suggests that the developmental increase may alternatively involve enhanced calcium-calmodulin-mediated mechanisms, increased expression of NO synthase, or greater availability of required cofactor(s). With an acute decline in Po2 in vitro from 680 to 150 or 40 mmHg, there was 50-88% attenuation of basal and acetylcholine-stimulated NO late in the third trimester and in the newborn but not early in the third trimester. Parallel studies of mesenteric endothelium revealed postnatal increases in basal and stimulated NO but no decline in NO at lower Po2. Ontogenic changes in endothelial NO production and in oxygen modulation of that process may be involved in the maturational decrease in vascular resistance and the development of oxygen responsiveness in the pulmonary circulation.

Regulation of endothelial nitric oxide synthase mRNA, protein, and activity during cell growth

1994 ◽  
Vol 267 (5) ◽  
pp. C1381-C1388 ◽  
Author(s):  
J. F. Arnal ◽  
J. Yamin ◽  
S. Dockery ◽  
D. G. Harrison
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Cell Growth ◽  
Endothelial Nitric Oxide Synthase ◽  
Northern Blot Analysis ◽  
No Synthase ◽  
Proliferating Cells ◽  
Bovine Endothelial Cells ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Cell growth influences the expression of several important tissue-specific functions. We sought to examine the effect of cell proliferation on nitric oxide (NO) synthase gene expression in cultured aortic bovine endothelial cells. Western and Northern blot analysis revealed three- and sixfold increases in NO synthase protein and mRNA, respectively, in growing compared with growth-arrested cells. The release of nitrogen oxides was also increased in proliferating cells compared with growth-arrested cells, as was the NO synthase activity assessed by L-arginine/L-citrulline conversion. Neither NO synthase inhibitors nor superoxide dismutase affected proliferation or thymidine incorporation, suggesting that increased NO release had no effect on endothelial cell growth. In conclusion, these studies demonstrate that expression of endothelial cell NO synthase is markedly increased in proliferating compared with quiescent nongrowing cells. The mechanisms underlying this and its physiological consequences remain to be defined.

scholarly journals Inactivation of Foxo3a and Subsequent Downregulation of PGC-1α Mediate Nitric Oxide-Induced Endothelial Cell Migration

2010 ◽  
Vol 30 (16) ◽  
pp. 4035-4044 ◽  
Author(s):  
Sara Borniquel ◽  
Nieves García-Quintáns ◽  
Inmaculada Valle ◽  
Yolanda Olmos ◽  
Brigitte Wild ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Protein Kinase ◽  
Endothelial Cell Migration ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Endothelial Migration ◽  
Endothelial Nitric Oxide

ABSTRACT In damaged or proliferating endothelium, production of nitric oxide (NO) from endothelial nitric oxide synthase (eNOS) is associated with elevated levels of reactive oxygen species (ROS), which are necessary for endothelial migration. We aimed to elucidate the mechanism that mediates NO induction of endothelial migration. NO downregulates expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), which positively modulates several genes involved in ROS detoxification. We tested whether NO-induced cell migration requires PGC-1α downregulation and investigated the regulatory pathway involved. PGC-1α negatively regulated NO-dependent endothelial cell migration in vitro, and inactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, which is activated by NO, reduced NO-mediated downregulation of PGC-1α. Expression of constitutively active Foxo3a, a target for Akt-mediated inactivation, reduced NO-dependent PGC-1α downregulation. Foxo3a is also a direct transcriptional regulator of PGC-1α, and we found that a functional FoxO binding site in the PGC-1α promoter is also a NO response element. These results show that NO-mediated downregulation of PGC-1α is necessary for NO-induced endothelial migration and that NO/protein kinase G (PKG)-dependent downregulation of PGC-1α and the ROS detoxification system in endothelial cells are mediated by the PI3K/Akt signaling pathway and subsequent inactivation of the FoxO transcription factor Foxo3a.

Characterization and localization of endothelial nitric oxide synthase using specific monoclonal antibodies

1993 ◽  
Vol 265 (5) ◽  
pp. C1379-C1387 ◽  
Author(s):  
J. S. Pollock ◽  
M. Nakane ◽  
L. D. Buttery ◽  
A. Martinez ◽  
D. Springall ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
No Synthase ◽  
Endothelial No Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We have produced specific monoclonal antibodies (MAb) against particulate bovine aortic endothelial nitric oxide synthase. In Western blots, native and cultured bovine aortic endothelial cells as well as cultured bovine microvascular endothelial cells possess immunoreactive NO synthase. In dot blots, MAb H210 and H32 detect 1 ng and 100 pg of purified endothelial NO synthase, respectively. Both antibodies are specific to the endothelial NO synthase and do not cross-react with other known isoforms of NO synthase, namely from the brain, from cytokine/endotoxin-induced macrophages, or from cytokine/endotoxin-induced vascular smooth muscle cells. Immunohistochemical studies demonstrated the specificity of endothelial NO synthase for endothelial cells in various bovine and human tissues. Many types of endothelial cells, macrovascular, microvascular, arterial, and venous were found to possess this specific isoform of NO synthase. Electron microscopy showed the enzyme to be associated with the plasma membrane, membranes of cytoplasmic vesicles, and in the cytoplasm in human umbilical vein endothelial cells. The results demonstrate that particulate endothelial NO synthase is present in a site to act rapidly to produce NO for release into the blood or toward the smooth muscle in many vascular beds.

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