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Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats

Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats

Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. Endothelial dysfunction is a major factor contributing to morbidity and…


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ProArgi 9 Is The Best Supplement for l'Arginine and Nitric Oxide Production Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats

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Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats

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Effect of L-Arginine and Aminoguanidine on Nitric Oxide and Renal Function in Diabetic Rats 4 To inve [bold]Objective[/bold] To investigate the effect of L-arginine 4 and aminoguanidine (AG) on serum nitric oxide (NO), 24 hr urinary protein excretion (UPE) of diabetic rats.


An enhanced production of nitric oxide (NO) from L-arginine, related to the diffuse expression of an inducible NO synthase (iNOS), contributes 4 the pathogenesis of 4 shock. Since адрес страницы activity depends on extracellular L-arginine, we hypothesized that limiting cellular L-arginine
Arginine supplementation 4 not affect plasma glucose levels in nondiabetic rats, but reduced body weight loss and plasma glucose 4 in diabetic rats.

Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats

Thus, dietary L-arginine supplementation stimulates endothelial NO synthesis by increasing BH 4 provision, which is beneficial for vascular function and glucose homeostasis in diabetic subjects.
Sodium nitroprusside, a nitric oxide donor, also showed significant inhibitory effect on 4 severity of diabetes induced by alloxan.

Alloxan treatment reduced nitric oxide generation, whereas l-arginine 4 sodium nitroprusside, when given along 4 alloxan, enhanced nitric oxide production to control values. Induction of diabetes by alloxan.
The present study was designed to evaluate the effects of l-arginine (l-arg) supplementation on blood pressure, vascular nitric oxide content, and renal morphometry in the adult offspring from.

Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats


The effects of L-arginine on the 4 are thought to 4 numerous. L-arginine, often referred to 4 as arginine, is an amino acid that can be produced by the body.

Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats

It is crucial 4 good health and proper physical function. L-arginine is involved in the synthesis of Nitric Oxide and creatine in.

Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats


Apr 30, 4 · Nitric oxide has been known to play a significant role 4 the pathophysiology of various disorders of the body. Ссылка its very short half-life, nitric oxide is 4 to modulate various neurotransmitter system(s) in the body and thus is speculated to play an imperative role in the pathogenesis of neurological disorders.


Arginine is also a precursor of nitric oxide, an essential compound and neurotransmitter that promotes blood circulation by dilating vessels and stimulates secretion of insulin.

Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats

As reported in the journal Diabetes Care, a team of researchers from the UK and Italy mounted a study to examine the effect of arginine on insulin sensitivity.
In an attempt to elucidate molecular mechanisms and factors involved in β cell regeneration, we evaluated a possible role of the l ‐arginine–nitric oxide (NO)‐producing pathway in alloxan‐induced diabetes mellitus.

Email: In an attempt to elucidate molecular mechanisms and factors involved in β cell regeneration, we evaluated a possible role of the l-arginine—nitric oxide NO -producing pathway in alloxan-induced diabetes mellitus.
Both non-diabetic and diabetic groups were additionally separated into three subgroups: i receiving l-arginine · HCl 2.
We found that disturbed glucose homeostasis, i.
Immunohistochemical findings revealed that l-arginine had a favourable effect on β cell neogenesis, i.
Moreover, confocal microscopy showed colocalization of insulin and pancreas duodenum homeobox-1 PDX-1 in both endocrine and exocrine pancreas.
This increase in insulin-expressing cells was accompanied by increased cell proliferation observed by proliferating cell nuclear antigen-PCNA 4 which occurred in a regulated manner since it was associated with increased apoptosis detected by the TUNEL method.
Furthermore, l-arginine enhanced both nuclear factor-kB NF-kB and neuronal nitric oxide synthase nNOS immunopositivities.
The effect of l-arginine on antioxidative defence was observed especially in restoring to control level the diabetes-induced increase in glutathione peroxidase activity.
In contrast to l-arginine, diabetic pancreas was not affected by l-NAME supplementation.
In conclusion, the results suggest beneficial l-arginine effects on alloxan-induced diabetes resulting from the stimulation of β cell neogenesis, including complex mechanisms of transcriptional and redox regulation.
Diabetes researchers have been searching intensively for ways to restore normal β cell mass in diabetic patients.
Current research interest is based on β cells regeneration by their proliferation or by neogenesis.
Neogenesis appears to occur in two phases, extensive proliferation of the non-insulin-producing progenitor cells followed by their differentiation.
In physiological conditions, the subtle balance between β cells mass renewal by replication and neogenesis and cell death apoptosis is of utmost importance for the maintenance of glucose homeostasis.
These processes are controlled by several transcription and humoral factors including pancreas duodenum homeobox-1, PDX-1.
PDX-1 represents a major regulator of pancreas development, β cells differentiation and function .
In adult endocrine pancreas, PDX-1 is primarily expressed in β cells, where it plays an important role in maintaining normal β cell function by regulating the expression of multiple genes, such as insulin, GLUT2 and glucokinase.
During fetal development, most of new β cells are formed by neogenesis.
In adult life, β cells are highly differentiated, with a low capacity for self-replication and it is difficult to detect neogenesis .
However, β cell neogenesis can be observed in several animal models after regeneration that has been provoked by challenging the endocrine tissue, including alloxan-induced diabetes mellitus .
However, time needed for endocrine pancreas recovery, as well as molecular mechanisms that trigger and control neogenesis are still incompletely understood.
On the other hand, it is clear that redox-sensitive cellular signalling pathways play important roles in the development, turnover and damaging of the β cells.
Furthermore, insulin secretion and also digestive enzymes synthesis and secretion from exocrine tissue are sensitive to the redox state of intracellular thiols, especially glutathione GSH .
Nitric oxide NO represents one of the signalling molecules involved in the modulation of the intracellular redox environment.
Besides, NO may regulate blood flowneurotransmission and exocrine secretion in pancreas.
All three isoforms 4 nitric oxide synthases, neuronal nNOSendothelial eNOS and inducible iNOSare expressed in pancreas.
It seems likely that specific tissue and cellular localization of the NOS isoform determines its role in the regulation of pancreatic functions.
Additionally to NOS, high level of arginase activity in the rat islet was reported.
Polyamines, the product of l-arginine metabolism by arginase, have been suggested to play a role in insulin biosynthesis and β cell replication.
Simultaneously, through arginine depletion, arginase controls NO production and regulates other arginine-dependent biological processes.
Increase of arginase activity ;as well as lower l-arginine and protein level ;was reported in the diabetic state.
Similarly, low circulating arginine due to increased arginase activity has been demonstrated in liver transplantationtrauma and sepsis associated with the decrease in T cell proliferation.
Moreover,have found that infusion of high doses of l-arginine results in a recovery of T cell function and number of CD4 + cells.
Also, l-arginine supplementation increases plasma urea and protein as well as arginine levels in diabetes and have been suggested to play a role in β cells regeneration in diabetic pancreas.
In addition, oral l-arginine administration reduced blood pressure in both normo- and hyperglycaemic conditions.
The effects of l-arginine in diabetes could be mediated by NO, as well.
However, the results on the role of NO in diabetes are contradictory.
In vitro studies showed that NO has по этому адресу properties causing destruction of pancreatic β cells, whereas NOS inhibitors may act as protectors .
This points to the role of NO in induction of type 1 diabetes.
However, relatively few in vivo studies have been focused on the role of NO in diabetes.
Some of them indicated that both NO and NO donors are favourable in diabetes mellitus.
The inhibition of the l-arginine effects by coadministration of NOS inhibitors was demonstrating in experimentally induced diabetes, suggesting NO-mediated mechanism of l-arginine action.
So have shown that simultaneous N ω-monomethyl- l-arginine l-NMMA treatment along with l-arginine of diabetic rats can completely block beneficial actions of l-arginine.
Moreover, the effect of l-NMMA was the same whether it was administrated alone or simultaneously with l-arginine.
In view of the above-mentioned data, we designed the study to examine the role of the l-arginine—NO-producing pathway in alloxan-induced diabetes mellitus.
Our attention was focused on possible NO effects on β cell neogenesis, especially transcriptional specific transcription factors: PDX-1, proliferating cell nuclear antigen-PCNA and nuclear factor-kB NF-kB and redox NOS isoforms and antioxidative defence regulation.
Male Mill Hill hybrid hooded, 3-month-old rats Rattus norvegicus, Berkenhout, 1769 were used.
They were divided into two groups: diabetic and non-diabetic rats.
Alloxan Sigma, Germany was applied to induce diabetes.
Both diabetic and non-diabetic groups were additionally separated into three subgroups.
One subgroup was receiving l-arginine 2.
The third subgroup served as a control.
Treatment of diabetic rats started after diabetes induction.
The rats were maintained in individual cages with food and water, i.
Each experimental group consisted of six animals.
After 12 days of treatment, blood glucose level was determined and the rats killed by decapitation.
The pancreas was dissected out within 3 min of death and thoroughly rinsed with physiological saline to remove traces of blood.
The homogenates were sonicated as described by.
Biochemical tests Blood was collected, allowed to clot and centrifuged 3500 g to prepare serum.
Serum insulin levels were estimated by radioimmmunoassay INEP, Belgrade, Serbia.
Serum total and HDL ссылка на продолжение lipoprotein cholesterol as well as triglyceride levels were determined by an autoanalyser Spectrum CCx, Abbott, Chicago, IL, USA.
LDL low-density lipoprotein -cholesterol was calculated from measured values of total cholesterol, triglyceride and HDL-cholesterol according to the Friedewald calculation.
Immunohistochemistry Immediately after dissection and washing, samples of pancreatic tissue were fixed in 10% formaldehyde at 4°C overnight and processed routinely for embedding in paraffin.
For single staining of only one antigen, 5 μm-thick sections were immunostained with the avidin—biotin—peroxidase method.
Insulin and PDX-1, as well as their colocalization were detected by confocal microscopy.
Insulin was detected with anti-insulin antibody 1: 1000; Abcam in combination with fluorescein isothiocyanate FITC -conjugated secondary antibody 1: 200; Abcam.
For PDX-1 staining, the slides were incubated with anti-PDX-1 antibody 1: 600; Abcam followed by incubation with Alexa Fluor 568-labelled secondary antibodies 1: 2000; Invitrogen, Paisley, UK.
Confocal images were acquired with a Carl Zeiss confocal laser scaning microscope LSM510 and a Windows NT operating system.
The examination of fluorescent immunolabelled samples was performed under Ar laser lamp FITC + Alexa Fluor 568 double-stained samples were excited with 488 nm and 543 nm light, respectively.
The specificity of the immune reaction, for both immunofluorescence and routine immunohistochemistry, was tested by replacing the primary antibody with a non-immune rabbit serum or by incubating the sections with the secondary antibody alone.
Apoptotic cell death detection transferase-mediated dUTP nick-end labelling-TUNEL technology Five micrometre thick pancreatic sections were used for immunohistochemical detection of apoptosis by TUNEL labelling of the nuclei showing specific oligonucleotide sequences resulting from DNA strand breaks.
Staining was Водяной полотенцесушитель TERMINUS Европа 32/20 П20 640x1030 with the DeadEnd Fluorometric TUNEL System Promega, Madison, USA according to the manufacturer's instructions.
For negative control, slides were incubated in the label solution only.
The positive control slides were treated with Dnase I before incubating in the TUNEL reaction mixture.
Determination of antioxidative defence Superoxide dismutase SOD activity was examined by the method of Misra and Fridovich.
Total SOD activity and manganese SOD Перейти activity after the inhibition with 4 m m KCN were measured and then copper, zinc SOD CuZnSOD activity calculated.
SOD units were defined as больше информации amount of the enzyme inhibiting adrenaline epinephrine auto-oxidation under appropriate reaction conditions.
The content of GSH was examined in the tissue after deproteinization with sulfosalicylic acid.
Other assays and statistics Protein content was estimated by the method of using bovine https://greenl66.ru/vanna/mashinka-dlya-strizhki-ovets-gts-2012.html albumin as a reference.
Analysis of variance ANOVA was applied for within-group comparison of the data.
If the F test showed an overall difference, Student's t test was used to evaluate significance of the differences.
Metabolic data summarizes the results of changes in body weight, food and fluid intake, blood glucose and serum insulin, total, HDL- LDL-cholesterol and trygliceride levels in non-diabetic and diabetic animals.
Non-diabetic groups of rats studied during 12 days showed an increase while all diabetic groups showed a decrease in their body weight.
Also, a significant increase was observed in food and fluid intake in all diabetic groups of rats compared with non-diabetic control.
Moreover, no decrease in insulin concentration as compared to non-diabetic control was observed.
These observations point to the beneficial effects of l-arginine treatment in diabetic rats.
No significant differences in HDL-cholesterol level were observed between the groups.
Changes of body weight, fluid and food intake, blood glucose and serum insulin, total, HDL- LDL-cholesterol and triglyceride levels in non-diabetic and diabetic rats Control l-Arginine l-NAME Group Non-diabetic Diabetic Non-diabetic Diabetic Non-diabetic Diabetic a Body weight changes g +43.
However, after l-arginine treatment, the area of islet insulin-immunopositive cells was increased and insulin staining appeared in surrounding exocrine tissue in diabetic animals suggesting β cells neogenesis as a result of l-arginine supplementation.
Furthermore, PDX-1 immunostaining has shown strong nuclear immunopositivity in this group of diabetic animals.
Also, analysis by double-immunostaining showed colocalization of insulin and PDX-1 in both endocrine and exocrine pancreas.
On the contrary, after l-NAME supplementation, no detectable changes in the patterns of insulin and PDX-1 immunopositivity were recorded in the diabetic group compared to diabetic control andrespectively.
Besides, in non-diabetic rats, l-arginine and l-NAME treatment did not significantly affect insulin immunopositivityrespectively compared to the non-diabetic control.
Immunohistochemical staining for PDX-1 in pancreas of non-diabetic control Adiabetic control Bl-arginine-treated Cdiabetes + l-arginine-treated Dl-NAME-treated Eand diabetes + l-NAME-treated rats F.
Strong PDX-1 staining can be seen in the cytoplasm and numerous nuclei of diabetic l-arginine-treated rats D.
узнать больше здесь bars, 20 μm.
Localization of insulin and PDX-1 by double immunofluorescence in pancreas of non-diabetic control A—Cdiabetic control J—Ll-arginine-treated D—Fdiabetes + l-arginine-treated M—Ol-NAME-treated G—I and diabetes + l-NAME-treated P—R rats.
Pancreas sections were double-labelled with anti-insulin and anti-PDX-1 antibodies, and нажмите чтобы увидеть больше analysed by a dual-channel confocal microscope.
Insulin and PDX-1 stainings appear as green A, D, G, J, M, P and red B, E, Детальнее на этой странице, K, N, Q fluorescence, respectively.
Colocalization results in the appearance of a yellow colour, seen only in diabetic l-arginine-treated rats O.
Scale bars, 20 μm.
To test whether restoration of β cells in diabetic pancreas was associated with proliferation of β cell precursors, pancreatic PCNA immunopositivity was examined.
The l-arginine-treated diabetic group was the only one among all examined groups with a strong PCNA immunopositivity in most nuclei in both endocrine and exocrine tissue.
Also, a mild staining with PCNA antibody was observed in the cytoplasm.
Similarly, a strong посетить страницу NF-kB immunopositivity was noticed only in diabetic l-arginine-treated ratsthe reaction product being detected in the cytoplasm, as well.
Immunohistochemical staining for NF-kB in pancreas of non-diabetic control Adiabetic control Bl-arginine-treated Cdiabetes + l-arginine-treated Dl-NAME-treated Eand diabetes + l-NAME-treated rats F.
Scale bars, 20 μm.
Immunohistochemical staining for PCNA in pancreas of non-diabetic control Adiabetic control Bl-arginine-treated Https://greenl66.ru/vanna/smesitel-dlya-vanni-s-dushem-rostovskaya-manufaktura-santehniki-sl115-142e-dvuhrichazhniy-leyka-v-ko.htmldiabetes + l-arginine-treated Dl-NAME-treated Eand diabetes + l-NAME-treated rats F.
The l-arginine-treated diabetic group was the only one among the examined groups with a прощения, Маршрутизатор Скетчбук Лиса FVS318 обычная nuclear PCNA staining D.
Scale bars, 20 μm.
L-Arginine acts to increase nNOS expression in diabetic pancreas nNOS immunopositivity was observed both in exocrine and endocrine tissue of non-diabetic control.
Immunoreaction of similar intensity in pancreatic cytoplasm and poor nuclear staining with nNOS antibody were detected in diabetic control.
On the contrary, eNOS immunopositivity in diabetic pancreas was unaffected see online while iNOS was significantly decreased see online by l-arginine.
The same treatment of non-diabetic animals revealed Отвертка аккумуляторная IVT CED Li-18 GK nNOS immunopositivity in the pancreas.
In contrast, l-NAME treatment did not significantly change pancreatic nNOS immunopositivity in diabetic animals compared to diabetic control.
Immunohistochemical staining for nNOS in pancreas of non-diabetic control Adiabetic control Bl-arginine-treated Cdiabetes + l-arginine-treated Dl-NAME-treated Eand diabetes + l-NAME-treated rats F.
Scale bars, 20 μm.
Formation of new β cells is accompanied by increased TUNEL immunopositivity Apoptotic TUNEL-positive nuclei were detected in pancreas of non-diabetic but not in diabetic control.
In contrast, no TUNEL positivity in non-diabetic rats was observed after l-arginine treatment, while some apoptotic nuclei were recorded in the pancreas of diabetic rats.
IRM-15-12 TUNEL-positive nuclei were seen in either non-diabetic or diabetic l-NAME-treated groups.
TUNEL detection of apoptosis in pancreas of non-diabetic control Adiabetic control Bl-arginine-treated Cdiabetes + l-arginine-treated Dl-NAME-treated Ediabetes + l-NAME-treated rats F.
Negative G and positive H controls are shown as well.
Apoptotic TUNEL-positive nuclei were observed in non-diabetic A but not на этой странице diabetic control rats B.
However, apoptotic nuclei can be seen in l-arginine-treated diabetic rats D.
Scale bars, 20 μm.
Pancreatic antioxidative defence Changes in pancreatic antioxidative defence are presented in.
It can be seen that GSH level was significantly higher in all diabetic groups than in the non-diabetic control with different ссылка на страницу significances.
Also, GSH level in diabetic l-arginine-treated rats showed a rising trend in comparison with diabetic control.
These effects are reflected at the biochemical level, i.
Also, immunohistochemical findings indicated beneficial effects of l-arginine on pancreatic tissue.
It is likely that exocrine cells transdifferentiated into the β cells since a strong PDX-1 immunopositivity, as well as its colocalization with insulin, was observed in exocrine cells.
Also, this process was accompanied by an increased PCNA immunopositivity suggesting an intense proliferation of the precursor cells.
It appears that the formation of new β cells is mediated by nNOS-derived NO and occurs in a regulated manner.
In contrast to l-arginine, diabetic pancreas was not affected by l-NAME supplementation.
Moreover, positive effects of NO in diabetic pancreas involved its role in the regulation of the tissue redox homeostasis, especially GSH level and GSH-Px activity.
We have found that l-arginine treatment was efficient in reducing a marked increase of blood glucose level in diabetic rats.
Besides, l-arginine treatment resulted in maintenance of insulin concentration close to normal level.
We have shown here that l-arginine significantly increased the area of insulin immunopositive β cells in endocrine tissue of diabetic pancreas.
Moreover, we have observed insulin expression in exocrine cells.
Recent studies demonstrated that differentiated exocrine cells взято отсюда a surprising plasticity and can transdifferentiate into different phenotypes, including hepatocyte-like and insulin-producing cells under appropriate conditions.
Our results suggest that NO could be one of the stimuli that induce transition блога Кружка 260-321 660 мл этом exocrine cells into endocrine β cells in diabetic pancreas.
This process appears to involve proliferation and differentiation of the exocrine cells.
The rate of proliferation assessed by PCNA labelling has shown the largest number of PCNA immunopositive nuclei in exocrine pancreas of diabetic l-arginine-treated rats reflecting the active process of proliferation.
The absolute dependency on l-arginine for cell proliferation and function was demonstrated in different model systems.
Similarly, we reported recently that l-arginine induces brown adipose tissue hyperplasia.
Also, l-arginine might play an important role in retina maturation through regulating proliferative phases in the early stages of rat postnatal development.
Our results can be connected to a recent report of who noticed increased ductal cells proliferation during islet regeneration in alloxan-induced diabetic rats treated with gastrin and epidermal growth factor.
We have also observed that transdifferentiated exocrine cells in diabetic pancreas of l-arginine-treated rats started to express transcription factor PDX-1.
PDX-1 immunopositivity was also strong in most of the pancreatic nuclei.
Since the activation of Мебель для ванной ASB-Mebel Терни 75 is associated with cytoplasm—nucleus translocationit could be hypothesized that NO-induced activation of PDX-1 occurred in diabetic pancreas.
Moreover, a strong colocalization of insulin and PDX-1 in exocrine tissue was detected in diabetic l-arginine-treated animals.
Coexpression of PDX-1 and insulin in the same population of the cells correlates well with the role PDX-1 plays in the regulation of insulin gene transcription.
Also, no similar effects of the treatment on normal rat pancreas were observed suggesting that the l-arginine—NO-producing pathway might be an important neogenesis factor in the case of conspicuous pancreatic remodelling, e.
Besides PCNA, NF-kB has been shown to act as a positive modulator of cell growth.
It has a specific function in the pancreas, i.
NF-kB, as a redox-sensitive transcription factor, appears to be regulated by NO.
The effect of NO on NF-kB activity depends on local NO concentration.
In the 4 study, l-arginine induced a strong NF-kB immunopositivity in numerous nuclei of diabetic pancreas.
This could mean that the stimulation of β cell neogenesis by l-arginine involved the activation of NF-kB, as well.
It seems likely that nNOS mediated these effects Профиль ARH-LINE-2448-2000 ANOD the l-arginine—NO-producing pathway, since a strong nNOS expression was observed in l-arginine-treated diabetic rats.
Besides, iNOS immunopositivity in diabetic pancreas was decreased while eNOS was not affected by l-arginine see online Supplemental material.
Besides ganglion cells and nerve fibres, nNOS is expressed in pancreatic exocrine and islet cells, as well.
Although thoroughly studied, its role in β cell function 4 still far from being completely understood.
Furthermore, reported that the regulation of glucokinase localization and activity in β cells is directly related to NO production and that association of glucokinase with secretory granules occurs through its interaction with nNOS.
These data suggest that the nNOS isoform is more conveniently situated to control insulin release than the 4, which is localized in the cytoplasm.
Along with the results of the present study, it seems that in addition to the physiological regulation of insulin secretion, nNOS, i.
Accumulating evidence obtained on various animal models showed that induction of β cell neogenesis leads to β cell expansion .
However, stimulation of β cell differentiation and their expansion have to be under homeostatic control.
In the present study, we have found that l-arginine-induced intensive formation of new β cells in diabetic pancreas occurred in a regulated manner since it was accompanied by apoptosis.
This ссылка in accordance with the data of who reported that in the presence of ongoing neogenesis, homeostatic regulatory mechanisms intervene to regulate β cell mass according to the prevailing metabolic requirements.
Thus, it could be hypothesized that the l-arginine—NO-producing pathway can control β cell turnover больше информации diabetes in order to restore disturbed glucose homeostasis.
The допускаете Ванна акриловая Bas ибица 1500х700 вам that requires further explanation is that l-arginine acted to decrease the insulin concentration in non-diabetic rats.
In contrast, the role of l-arginine as insulin secretagogue has been well documented in numerous in vitro and in vivo studies.
However, many studies in which NOS activity was manipulated by NO donors or NOS substrates give controversial data about NO нажмите сюда on islet hormone release.
Moreover, we have found that changes in insulin level in l-NAME-treated non-diabetic rats had the same trend as those observed in l-arginine-receiving rats.
Many authors suggest controversial and surprising effects of NOS inhibitors on insulin release.
Namely, depending on the concentration and the nature of the enzyme antagonist used, NOS inhibition has been reported to produce an inhibitory effect ;a stimulatory effect ; or no effect at all ; on insulin secretion.
Also, there are the differences between data from in vitro and in vivo studies.
Namely, additionally to the inhibition of NOS, in vivo supplementation with NOS inhibitors may exert systemic effects such as vasoconstriction or interfere with neuronal mechanisms that could affect insulin release.
Furthermore, NOS inhibition may also cause an increase in islet capillary blood flow.
Also, it is known from other tissues ; that some NOS inhibitors, in certain concentrations and experimental conditions, might in fact stimulate NO production.
Hence, it seems indispensable to perform analyses of islet NOSs when assessing the effects of NOS substrate and NOS inhibitors on insulin secretion.
In that context, we have shown a decrease in nNOS as well as unchanged iNOS and eNOS immunopositivities in l-arginine-treated non-diabetic rats.
Besides, l-NAME treatment induced a decrease in the immunopositivity of all three NOS isoforms.
These observations favour the assumption that NO acts as a positive modulator of insulin release.
An exciting finding of this study was also that both l-arginine and l-NAME treatments reduced body weight gain in non-diabetic rats compared with the non-diabetic control.
Since this is consistent with a decrease in insulin level, it is likely that lower body weight gain in both these groups compared with non-diabetic control represents the result of impaired anabolic effects of insulin.
A number of studies have shown that disturbed redox homeostasis and oxidative stress are implicated in the aetiology of diabetes mellitus, as well as in late pathological complications associated with this disease.
In alloxan-induced diabetes, reactive oxygen species generation and disturbed redox homeostasis in β cells take place due to alloxan entrance into the GSH-mediated redox cycle.
Moreover, chronic hyperglycaemia and elevated free fatty acids, characteristic of diabetes, significantly contribute to oxidative stress in many tissues including pancreas.
Considering these facts, it could be supposed that increased GSH-Px activity, as well as enhanced level of its cofactor GSH observed in diabetic pancreas, represents an adaptive response to peroxidative pressure, i.
Such a response of the GSH-dependent part of antioxidative defence is of utmost importance for the maintenance of redox homeostasis and thus, normal pancreas functioning.
Our results demonstrating the NO involvement in the regulation of https://greenl66.ru/vanna/vobler-ima-komomo-ii-90-z1617.html homeostasis in diabetic pancreas further support our hypothesis on the protective effects of the l-arginine—NO-producing pathway in diabetes.
Firstly, GSH-Px activity in diabetic l-arginine-treated rats was maintained near control levels.
Similarly, reported that l-arginine, as a NOS substrate, and sodium nitroprusside, a NO donor, acted to restore GSH-Px activity close to control levels in erythrocytes of alloxan-induced diabetes.
Furthermore, GSH content in the pancreas of 4 rats expressed an increasing trend upon l-arginine treatment.
Interrelationship of NO and GSH has been previously reported by others.
It should be mentioned also that have shown that GSSG formation was accompanied by a rise in total glutathione level.
In summary, the present study provides evidence of multiple beneficial effects of the l-arginine—NO-producing pathway in alloxan-induced diabetes mellitus.
These effects resulted from the promotion of events that lead to returning diabetic pancreatic tissue to homeostasis including the 4 of β cell neogenesis through the activation of the transcription factors involved PDX-1, PCNA and NF-kB.
Our results also point to the role nNOS plays in the mechanisms involved in these processes.
However, additional studies are necessary for their full elucidation.
Our efforts along these lines are in progress.
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Aly Omnia Effect of L-Arginine on Nitric Oxide Synthesis in Diabetic Rats

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