STUDY THE LEVEL OF ARGINASE ACTIVITY AND ITS CORRELATION WITH LIVER AND KIDNEY FUNCTIONS FOR PATIENTS WITH TYPE-2 DIABETES IN NINEVEH GOVERNORATE

We recently showed that red blood cells (RBCs) from patients with type 2 diabetes mellitus (T2DM-RBCs) induce endothelial dysfunction through a mechanism involving arginase I and reactive oxygen species. Peroxynitrite is known to activate arginase in endothelial cells. Whether peroxynitrite regulates arginase activity in RBCs, and whether it is involved in the cross-talk between RBCs and the vasculature in T2DM, is unclear and elusive. The present study was designed to test the hypothesis that endothelial dysfunction induced by T2DM-RBCs is driven by peroxynitrite and upregulation of arginase. RBCs were isolated from patients with T2DM and healthy age matched controls. RBCs were co-incubated with aortae isolated from wild type rats for 18 h in the absence and presence of peroxynitrite scavenger FeTTPS. Evaluation of endothelial function in organ chambers by cumulative addition of acetylcholine as well as measurement of RBC and vessel arginase activity was performed. In another set of experiments, RBCs isolated from healthy subjects (Healthy RBCs) were incubated with the peroxynitrite donor SIN-1 with subsequent evaluation of endothelial function and arginase activity. T2DM-RBCs, but not Healthy RBCs, induced impairment in endothelial function, which was fully reversed by scavenging of RBC but not vascular peroxynitrite with FeTPPS. Arginase activity was up-regulated by the peroxynitrite donor SIN-1 in Healthy RBCs, an effect that was inhibited by FeTTPS. Healthy RBCs co-incubated with aortae in the presence of SIN-1 caused impairment of endothelial function, which was inhibited by FeTTPS or the arginase inhibitor ABH. T2DM-RBCs induced up-regulation of vascular arginase, an effect that was fully inhibited by FeTTPS. Collectively, our data indicate that RBCs impair endothelial function in T2DM via an effect that is driven by a peroxynitrite-mediated increase in arginase activity. This mechanism may be targeted in patients with T2DM for improvement in endothelial function.

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Abstract 378: Red Blood Cells From Patients With Type 2 Diabetes Induce Endothelial Dysfunction Through Up-Regulation of Arginase I

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.378 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Zhichao Zhou ◽

Ali Mahdi ◽

Yahor Tratsiakovich ◽

Oskar Kövamees ◽

Jiangning Yang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Endothelial Dysfunction ◽

Red Blood Cells ◽

Blood Cells ◽

Arginase Activity ◽

Diabetic Patients ◽

Functional Evaluation ◽

Mammary Arteries ◽

Arginase I

We previously showed that increased arginase activity is a key mechanism for endothelial dysfunction in patients with type 2 diabetes mellitus (T2DM) thereby arginase inhibition improves endothelial function. Recently, we demonstrated a crucial role of red blood cells (RBCs) in control of cardiac function via an arginase-dependent regulation of nitric oxide export from RBCs, suggesting a direct interaction of RBCs with cardiovascular function. Considering an increase in arginase activity in T2DM, we hypothesized that RBCs induce endothelial dysfunction in T2DM via up-regulated arginase I. Healthy rat aortas were incubated with RBCs from patients with T2DM (T2DM-RBCs) and age-matched healthy subjects (H-RBCs) for 18 h in the absence and presence of the arginase inhibition or scavenging of reactive oxygen/nitrogen species (ROS/RNS). Following the incubation, endothelium-dependent and -independent relaxations (EDR and EIR) were determined using wire myograph. Human internal mammary arteries (IMAs) obtained from non-diabetic patients who underwent cardiac surgery were also incubated with RBCs for functional evaluation. Arginase activity and protein expression were determined in RBCs. EDR was impaired in vessels incubated with T2DM-RBCs (Emax: 43.2±3.0% in aortas, n=8; 32.3±2.7% in IMAs, n=3) but not H-RBCs (Emax: 74.3±3.4% in aortas; 71.5±5.1% in IMAs) in comparison with buffer (Emax: 74.4±2.3% in aortas; 73.1±5.0% in IMAs; P<0.01 vs. T2DM-RBCs). EIR was not affected by T2DM-RBCs. The impairment in EDR in rat aortas was fully reversed by inhibition of arginase, ROS and RNS in RBCs. Arginase activity was significantly elevated in T2DM-RBCs. The increased arginase activity was attributed to arginase I, as there was increased arginase I expression in RBCs, whereas no arginase II expression was detected. Moreover, high glucose and RNS stimulation increased arginase activity in H-RBCs, while ROS/RNS scavenging decreased arginase activity in T2DM-RBCs. This study demonstrates a novel mechanism behind endothelial dysfunction that T2DM-RBCs induce endothelial dysfunction via ROS/RNS-dependent up-regulation of arginase I. Targeting arginase I in RBCs may serve as a novel therapeutic tool for treatment of endothelial dysfunction in T2DM.

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Determining the Pancreatic Arginase Activity and a-Amylase Levels in Patients with Type 2 Diabetes and Alcoholic Pancreatitis

Challenging Issues on Environment and Earth Science Vol. 5 ◽

10.9734/bpi/ciees/v5/9804d ◽

2021 ◽

pp. 12-20

Author(s):

José D. Méndez ◽

Roberto De Haro ◽

Verna Méndez-Valenzuela ◽

Jorge L. Ble-Castillo ◽

Hector O. Rubio

Keyword(s):

Type 2 Diabetes ◽

Arginase Activity ◽

Alcoholic Pancreatitis

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Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: effects on hepatic peroxisome proliferator-activated receptor-gamma receptors

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2017-0533 ◽

2018 ◽

Vol 96 (5) ◽

pp. 485-497 ◽

Cited By ~ 6

Author(s):

Samah M. Elaidy ◽

Mona A. Hussain ◽

Mohamed K. El-Kherbetawy

Keyword(s):

High Fat Diet ◽

Time Dependent ◽

Peroxisome Proliferator ◽

High Fat ◽

Peroxisome Proliferator Activated Receptor ◽

Ppar Γ ◽

Liver And Kidney ◽

Kidney Functions ◽

Dm Type 2

Targeting peroxisome proliferator-activated receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for diabetes mellitus (DM) type 2. The PPAR-γ modulators display improvements in the insulin-sensitizing and adverse effects of the traditional thiazolidinediones. Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand with agonistic post-transcriptional effects. Currently, NTZ antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin rat model of type 2 diabetes was explored. Diabetic adult male Wistar rats were treated orally with either PIO (2.7 mg·kg−1·day−1) or NTZ (200 mg·kg−1·day−1) for 14, 21, and 28 days. Body masses, fasting blood glucose, IR, lipid profiles, and liver and kidney functions of rats were assayed. Hepatic glucose metabolism and PPAR-γ protein expression levels as well as hepatic, pancreatic, muscular, and renal histopathology were evaluated. Significant time-dependent euglycemic and insulin-sensitizing effects with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase enzymes and PPAR-γ protein expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM type 2. Further systematic NTZ/PPAR-γ receptor subtype molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.

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Analysis of liver and kidney function test results and clinical value in 1000 patients with type 2 diabetes mellitus

10.47939/mh.v1i1.12 ◽

2020 ◽

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Kidney Function ◽

Test Results ◽

Clinical Value ◽

Kidney Function Test ◽

Function Test ◽

Liver And Kidney

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L-Citrulline Supplementation Increases Plasma Nitric Oxide Levels and Reduces Arginase Activity in Patients With Type 2 Diabetes

Frontiers in Pharmacology ◽

10.3389/fphar.2020.584669 ◽

2020 ◽

Vol 11 ◽

Author(s):

Alia Shatanawi ◽

Munther S. Momani ◽

Ruaa Al-Aqtash ◽

Mohammad H Hamdan ◽

Munir N. Gharaibeh

Keyword(s):

Nitric Oxide ◽

Type 2 Diabetes ◽

Endothelial Cells ◽

Vascular Dysfunction ◽

Arginase Activity ◽

Diabetic Patients ◽

No Production ◽

Major Contributor ◽

Therapeutic Benefits

Type 2 diabetes mellitus (T2DM) is becoming a major contributor to cardiovascular disease. One of the early signs of T2DM associated cardiovascular events is the development of vascular dysfunction. This dysfunction has been implicated in increasing the morbidity and mortality of T2DM patients. One of the important characteristics of vascular dysfunction is the impaired ability of endothelial cells to produce nitric oxide (NO). Additionally, decreases in the availability of NO is also a major contributor of this pathology. NO is produced by the activity of endothelial NO synthase (eNOS) on its substrate, L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence, increases in arginase activity can decrease arginine levels, reducing its availability to eNOS and decreasing NO production. Diabetes has been linked to elevated arginase and associated vascular endothelial dysfunction. We aimed to determine levels of plasma NO and arginase activity in (T2DM) patients and the effects of L-citrulline supplementation, a natural arginase inhibitor, on inhibiting arginase activity in these patients. Levels of arginase correlated with HbA1c levels in diabetic patients. Twenty-five patients received L-citrulline supplements (2000 mg/day) for 1 month. Arginase activity decreased by 21% in T2DM patients after taking L-citrulline supplements. Additionally, plasma NO levels increased by 38%. There was a modest improvement on H1Ac levels in these patients, though not statistically significant. The effect of L-citrulline on arginase activity was also studied in bovine aortic endothelial cells (BAECs) grown in high glucose (HG) conditions. HG (25 mM, 72 h) caused a 2-fold increase in arginase activity in BAECs and decreased NO production by 30%. L-citrulline (2.5 mM) completely prevented the increase in arginase activity and restored NO production levels. These data indicate that L-citrulline can have therapeutic benefits in diabetic patients through increasing NO levels and thus maintaining vascular function possibly through an arginase inhibition related pathway.

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Relationship between Thyroid Function and Kidney Function in Patients with Type 2 Diabetes

International Journal of Endocrinology ◽

10.1155/2018/1871530 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Ying Zhang ◽

Yang Wang ◽

Xiao Jun Tao ◽

Qian Li ◽

Feng Fei Li ◽

...

Keyword(s):

Type 2 Diabetes ◽

Thyroid Function ◽

Subclinical Hypothyroidism ◽

Thyroid Dysfunction ◽

Urine Albumin ◽

High Incidence ◽

Lower Egfr ◽

Incidence Of Ckd ◽

Kidney Functions

Purpose. To determine if the TSH is related to estimated glomerular filtration rate (eGFR) in T2D patients without overt thyroid dysfunction. Methods. A cohort study of 5936 T2D patients was assessed for thyroid and kidney functions, in whom 248 with subclinical hyperthyroidism and 362 with subclinical hypothyroidism. Serum creatinine and 24-hour urine albumin excretion (UAE) were collected. Chronic kidney disease (CKD) was defined as eGFR < 60 ml/min/1.73 m2. Results. Compared with euthyroid subjects, the patients with subclinical hypothyroidism had lower eGFR (82.7 ± 22.4 vs. 90.5 ± 22.4 ml/min/1.73 m2, p<0.01), higher UAE (114 ± 278 vs. 88 ± 229 mg/24 h, p<0.05), and high incidence of CKD (16.0% vs. 10.1%, p<0.05). The participants with a TSH level between 0.55 and 3.0 μIU/ml had a higher eGFR (91.4 ± 22.2 ml/min/1.73 m2) and a lower prevalence of CKD (9.5%) than those with higher TSH (3.01–4.78 μIU/ml, 85.6 ± 22.7 ml/min/1.73 m2, p<0.01 and 13.1%, p<0.01). Linear logistic regression analysis showed that the eGFR was significantly negatively associated with TSH (OR: 0.519, 95% CI: 0.291–0.927, p<0.05), after adjustment of confounders. Conclusion. High TSH was independently associated with decreased eGFR in type 2 diabetes patients without overt thyroid dysfunction. Our findings indicate that doctors who treat T2D patients should routinely measure the thyroid function.

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Efficacy and safety of a combination of miglitol, metformin and insulin aspart in the treatment of type 2 diabetes

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v20i10.22 ◽

2021 ◽

Vol 20 (10) ◽

pp. 2171-2177

Author(s):

Tingyu Ke ◽

Guoliang Cheng ◽

Liping Tan ◽

Xiangming Zhou ◽

Yuanyuan Miao ◽

...

Keyword(s):

Blood Sugar ◽

Insulin Aspart ◽

Treatment Options ◽

Combined Treatment ◽

Sensory Neuropathy ◽

Liver And Kidney ◽

Sugar Levels ◽

Medical University ◽

Kidney Functions

Purpose: To study the clinical effect of combining insulin aspart with different drugs in the treatment oftype 2 diabetes mellitus (T2DM).Methods: Two hundred and thirty-seven T2DM patients admitted to the Endocrinology Department of the Second Affiliated Hospital of Kunming Medical University from March to September 2018 were selected as subjects in this study. Miglitol and metformin were used in combination with insulin aspart in the treatment of T2DM. In addition, data on the effectiveness and safety of different treatment options,such as patient’s weight, waist circumference, blood glucose indicators, indices of heart, liver and kidney functions, and incidence of complications were recorded and compared between the two groups.Results: The use of a combination of miglitol and insulin aspart produced an excellent hypoglycaemic effect, and it significantly reduced the incidence of sensory neuropathy in the eyes and distal limbs (p < 0.05). The use of combination of metformin and insulin aspart effectively protected the heart and kidney, and prevented hypoglycaemia (p < 0.05).Conclusion: These results suggest that treatment with a combination of miglitol and insulin aspart is suitable for patients with T2DM whose blood sugar levels are out of control, while combined treatment with metformin and insulin aspart is more suited for patients who desire to reduce blood sugar and blood lipids through weight loss, and patients with cardiac and renal insufficiency.

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