New Insight into the Role of Nitric Oxide Pathways in Pancreas

Buchwalow, Igor; Schnekenburger, Jürgen; Samoilova, Vera; Boecker, Werner; Neumann, Joachim; Tiemann, Katharina

doi:10.1267/ahc.18028

Cited by 14 publications

(10 citation statements)

References 44 publications

(72 reference statements)

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“…As a result, the cell is getting short of bioactive NO and responses daespite of upregulation of NOS and guanylyl cyclase. 33 In the present study, the brain tissue level of NO was significantly increased; however, the cGMP level was decreased in the AD group compared to the control group. This finding implies high production of iNOS-derived NO which exerted the nitrostive effect with little physiological effect mainfested by the decreased cGMP level that may be secondary to upregulation of PDEs.…”

Section: Discussioncontrasting

confidence: 52%

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Sildenafil ameliorates Alzheimer disease via the modulation of vascular endothelial growth factor and vascular cell adhesion molecule-1 in rats

et al. 2020

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Alzheimer disease (AD) is a chronic neurodegenerative disease with multi-pathways pathogenesis. Sildenafil is a selective phosphodiesterase-5 inhibitor with a potential benefit in the treatment of AD. This study investigated the possible mechanisms underlying the effect of sildenafil in AD with emphasis on vascular endothelial growth factor (VEGF), and vascular cell adhesion molecule-1 (VCAM-1). Twenty-four adult male rats were classified into four groups; control group: received vehicles, sildenafil–control: received sildenafil (15 mg/kg/day, p.o.), AD group received Aluminum (25 mg/kg/day, p.o.), AD-treated group: received sildenafil (15 mg/kg/day, p.o.) for 6 weeks. AD was assessed by memory performance test and confirmed by histopathological examination and immunostaining of, neurogenesis marker nestin and α-synuclein. The levels of VEGF-A, VCAM-1, oxidative stress markers and TNF-α in brain tissue were evaluated. AD rats showed histopathological evidences of AD; along with increased latency time in the memory test. There was a decrease in VEGF-A, and an increase in VCAM-1, TNF-α, and oxidative stress markers. Immunohistochemical study showed a significant increase in α-synuclein and a significant decrease in nestin expressions in brain tissues. Sildenafil administration ameliorated the histopathological changes and decreased latency time. Such effect was associated with a decrease in VCAM-1, TNF-α and oxidative stress as well as an increase in VEGF-A. Sildenafil caused a significant increase in nestin and a decrease in α-synuclein immunostaining. These findings suggested a protective effect of sildenafil via modulation of VEGF-A, and VCAM-1.

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Section: Discussioncontrasting

confidence: 52%

“…At this point, the NO message may be interrupted. 33 NO, in oxidative stress and inflammatory conditions, can react with superoxide radical (O2-) to produce reactive oxygen species and reactive nitrogen species. Therefore, NO can damage the cell of its origin and cause a variety of diseases including AD.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil ameliorates Alzheimer disease via the modulation of vascular endothelial growth factor and vascular cell adhesion molecule-1 in rats

et al. 2020

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“…Although, NO plays essential role in several physiological processes, nonetheless, if it accumulates, it can react with superoxide anion to produce toxic nitrite anion, thereby causing tissue damage. 43 Thus, the apparent suppression of NaF-mediated increase in NO concentration by resveratrol further suggests its anti-inflammatory property.…”

Section: Discussionmentioning

confidence: 98%

Protective role of resveratrol, a natural polyphenol, in sodium fluoride-induced toxicity inDrosophila melanogaster

Abolaji

Ajala

Adigun

et al. 2019

Exp Biol Med (Maywood)

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Sodium fluoride (NaF) is used in water fluoridation and dental products such as mouth rinses and toothpastes. Resveratrol is a natural polyphenol with antioxidant and anti-inflammatory properties. The present study was carried out to evaluate the toxicity of NaF and the protective role of resveratrol in Drosophila melanogaster. For longevity assay, Harwich strain of D. melanogaster was treated with NaF (0, 10, 30, 50, 70 and 90 mg/kg diet) throughout the lifespan and daily mortality recorded. Then, flies were again treated with similar doses of NaF for seven days to evaluate survival rate and oxidative stress markers. Thereafter, 60 mg resveratrol/kg diet was selected to determine its ameliorative role in NaF (70 mg/kg)-induced toxicity in flies: Group A (control), Group B (60 mg resveratrol/kg diet), Group C (70 mg NaF/kg diet), and Group D (resveratrol, 60 mg/kg diet) + NaF, 70 mg/kg diet). Thereafter, Glutathione-S-transferase (GST), catalase and acetylcholinesterase (AchE) activities, as well as total thiol (T-SH), nitrites/nitrates and hydrogen peroxide (H2O2) levels were determined. The results showed that resveratrol prevented NaF-induced elevation of H2O2 and nitrites/nitrates levels, as well as catalase activity. In addition, resveratrol restored NaF-induced inhibition of GST and AChE activities and depletion of T-SH content ( P < 0.05). Conclusively, resveratrol offered protective benefit against NaF-mediated toxicity in flies due to its antioxidant and anti-inflammatory properties. Impact statement D. melanogaster was used to understand the impact of NaF on lifespan and emergence rate as well as the rescue role of resveratrol. These parameters are difficult to carry out in previously used models such as rodents. This further enforces in part, the suitability of D. melanogaster in studying NaF-induced toxicity and the therapeutic effects of drugs. Additionally, we found that resveratrol rescued D. melanogaster from oxidative stress-induced by sodium fluoride (NaF) administration. This study is of public health significance as it indicated that the consumption of fruits rich in resveratrol such as grapes may offer protective role against inadvertent exposure to NaF and related chemicals.

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“…The expression of NOS 3 was increased in response to the presence of a NO donor, and this effect was concentration-dependent suggesting that the inhibitory effects of NO donor on survival and secretory function of β cells may be partially mediated by increased levels of NOS 3 . Although the involvement of different NOS isoforms in regulation of insulin secretion is controversial, several reports have demonstrated that NOS 3 and NOS 1 are constitutively expressed in pancreatic vasculature and neurons, respectively [ 7 ]. Compared with other isoforms, NOS 3 seems to play a major role in modulation of pancreatic secretion and has been detected in rat and human pancreatic islets; hence, the present study focused on the involvement of NOS 3 in this process [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although the involvement of different NOS isoforms in regulation of insulin secretion is controversial, several reports have demonstrated that NOS 3 and NOS 1 are constitutively expressed in pancreatic vasculature and neurons, respectively [7]. Compared with other isoforms, NOS 3 seems to play a major role in modulation of pancreatic secretion and has been detected in rat and human pancreatic islets; hence, the present study focused on the involvement of NOS 3 in this process [7].…”

Section: Protein Expression Of Cholinergic Receptors In the Presence mentioning

confidence: 94%

Nitric oxide interacts with cholinoceptors to modulate insulin secretion by pancreatic β cells

Mussa

Srivastava

Mohammed

et al. 2020

Pflugers Arch - Eur J Physiol

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Dysfunction of the pancreatic β cells leads to several chronic disorders including diabetes mellitus. Several mediators and mechanisms are known to be involved in the regulation of β cell secretory function. In this study, we propose that cytokine-induced nitric oxide (NO) production interacts with cholinergic mechanisms to modulate insulin secretion from pancreatic β cells. Using a rat insulinoma cell line INS-1, we demonstrated that β cell viability decreases significantly in the presence of SNAP (NO donor) in a concentration- and time-dependent manner. Cell viability was also found to be decreased in the presence of a combined treatment of SNAP with SMN (muscarinic receptor antagonist). We then investigated the impact of these findings on insulin secretion and found a significant reduction in glucose uptake by INS-1 cells in the presence of SNAP and SMN as compared with control. Nitric oxide synthase 3 gene expression was found to be significantly reduced in response to combined treatment with SNAP and SMN suggesting an interaction between the cholinergic and nitrergic systems. The analysis of gene and protein expression further pin-pointed the involvement of M3 muscarinic receptors in the cholinergic pathway. Upon treatment with cytokines, reduced cell viability was observed in the presence of TNF-α and IFN-γ. A significant reduction in insulin secretion was also noted after treatment with TNF-α and IFN-γ and IL1-β. The findings of the present study have shown for the first time that the inhibition of the excitatory effects of cholinergic pathways on glucose-induced insulin secretion may cause β cell injury and dysfunction of insulin secretion in response to cytokine-induced NO production.

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New Insight into the Role of Nitric Oxide Pathways in Pancreas

Cited by 14 publications

References 44 publications

Sildenafil ameliorates Alzheimer disease via the modulation of vascular endothelial growth factor and vascular cell adhesion molecule-1 in rats

Sildenafil ameliorates Alzheimer disease via the modulation of vascular endothelial growth factor and vascular cell adhesion molecule-1 in rats

Protective role of resveratrol, a natural polyphenol, in sodium fluoride-induced toxicity inDrosophila melanogaster

Nitric oxide interacts with cholinoceptors to modulate insulin secretion by pancreatic β cells

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