Normal Ca2+ extrusion by the Ca2+ pump of intact red blood cells exposed to high glucose concentrations

2001 ◽  
Vol 280 (6) ◽  
pp. C1449-C1454 ◽  
Author(s):  
Julia E. Raftos ◽  
Amanda Edgley ◽  
Robert M. Bookchin ◽  
Zipora Etzion ◽  
Virgilio L. Lew ◽  
...  
Keyword(s):  
High Glucose ◽  
Diabetic Rats ◽  
Maximal Velocity ◽  
Glucose Levels ◽  
Normal Human ◽  
Streptozotocin Diabetic Rats ◽  
The Mean ◽  
Human Rbcs

The ATPase activity of the plasma membrane Ca2+ pump (PMCA) has been reported to be inhibited by exposure of red blood cell (RBC) PMCA preparations to high glucose concentrations. It has been claimed that this effect could have potential pathophysiological relevance in diabetes. To ascertain whether high glucose levels also affect PMCA transport function in intact RBCs, Ca2+extrusion by the Ca2+-saturated pump [PMCA maximal velocity ( V max)] was measured in human and rat RBCs exposed to high glucose in vivo or in vitro. Preincubation of normal human RBCs in 30–100 mM glucose for up to 6 h had no effect on PMCA V max. The mean V max of RBCs from 15 diabetic subjects of 12.9 ± 0.7 mmol · 340 g Hb−1 · h−1 was not significantly different from that of controls (14.3 ± 0.5 mmol · 340 g Hb−1 · h−1). Similarly, the PMCA V max of RBCs from 11 streptozotocin-diabetic rats was not affected by plasma glucose levels more than three times normal for 6–8 wk. Thus exposure to high glucose concentrations does not affect the ability of intact RBCs to extrude Ca2+.

scholarly journals Spironolactone improves nephropathy by enhancing glucose-6-phosphate dehydrogenase activity and reducing oxidative stress in diabetic hypertensive rat

2011 ◽  
Vol 13 (1) ◽  
pp. 56-66 ◽  
Author(s):  
Bruno S Pessôa ◽  
Elisa BMI Peixoto ◽  
Alexandros Papadimitriou ◽  
Jacqueline M Lopes de Faria ◽  
José B Lopes de Faria
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
High Glucose ◽  
Diabetic Rats ◽  
G6pd Activity ◽  
Spontaneously Hypertensive ◽  
Glucose Levels ◽  
Glucose 6 Phosphate Dehydrogenase

Spironolactone (SPR), a mineralocorticoid receptor blocker, diminishes hyperglycemia-induced reduction in glucose-6-phosphate dehydrogenase (G6PD) activity, improving oxidative stress damage. This study investigated whether SPR ameliorates nephropathy by increasing G6PD activity and reducing oxidative stress in spontaneously hypertensive diabetic rats (SHRs). The streptozotocin-induced diabetic rats received or not SPR 50 mg/kg per day, for eight weeks. A human mesangial cell line was cultured in normal or high glucose conditions, with or without SPR, for 24 h. Plasma glucose levels and systolic blood pressure were unaltered by diabetes or by SPR treatment. Albuminuria, fibronectin expression, 8-OHdG urinary levels, lipid peroxidation and p47phox expression were higher in the diabetic rats compared with the control and were reduced by SPR. The antioxidant GSH/GSSG ratio was reduced in the diabetic rats and the treatment reestablished it. Diabetes-induced SGK1 up-regulation was inhibited by SPR. Reactive oxygen species (ROS) and superoxide production induced by NADPH oxidase were increased by hyperglycemia and high glucose, in vivo and in vitro, respectively, and were reduced with SPR. Hyperglycemia and high glucose decreased G6PD activity, which was restored with SPR. These results suggest that SPR ameliorates nephropathy in diabetic SHRs by restoring G6PD activity and diminishes oxidative stress without affecting glycaemia and blood pressure.

scholarly journals Maintaining a Physiological Blood Glucose Level with ‘Glucolevel’, a Combination of Four Anti-Diabetes Plants Used in the Traditional Arab Herbal Medicine

2008 ◽  
Vol 5 (4) ◽  
pp. 421-428 ◽  
Author(s):  
Omar Said ◽  
Stephen Fulder ◽  
Khaled Khalil ◽  
Hassan Azaizeh ◽  
Eli Kassis ◽  
...  
Keyword(s):  
Juglans Regia ◽  
Human Fibroblasts ◽  
Tolerance Test ◽  
Positive Control ◽  
Diabetic Rats ◽  
Yeast Cells ◽  
Sugar Uptake ◽  
Glucose Levels

Safety and anti-diabetic effects of Glucolevel, a mixture of dry extract of leaves of theJuglans regiaL,Olea europeaL,Urtica dioicaL andAtriplex halimusL were evaluated usingin vivoandin vitrotest systems. No sign of toxic effects (using LDH assay) were seen in cultured human fibroblasts treated with increasing concentrations of Glucolevel. Similar observations were seenin vivostudies using rats (LD50: 25 g/kg). Anti-diabetic effects were evidenced by the augmentation of glucose uptake by yeast cells (2-folds higher) and by inhibition of glucose intestinal absorption (∼49%) in a rat gut-segment. Furthermore, treatment with Glucolevel of Streptozotocin-induced diabetic rats for 2–3 weeks showed a significant reduction in glucose levels [above 400 ± 50 mg/dl to 210 ± 22 mg/dl (P< 0.001)] and significantly improved sugar uptake during the glucose tolerance test, compared with positive control. In addition, glucose levels were tested in sixteen human volunteers, with the recent onset of type 2 diabetes mellitus, who received Glucolevel tablets 1 × 3 daily for a period of 4 weeks. Within the first week of Glucolevel consumption, baseline glucose levels were significantly reduced from 290 ± 40 to 210 ± 20 mg/dl. At baseline, a subgroup of eleven of these subjects had glucose levels below 300 mg% and the other subgroup had levels ≥ 300 mg%. Clinically acceptable glucose levels were achieved during the 2–3 weeks of therapy in the former subgroup and during the 4th week of therapy in the latter subgroup. No side effect was reported. In addition, a significant reduction in hemoglobin A1C values (8.2 ± 1.03 to 6.9 ± 0.94) was found in six patients treated with Glucolevel. Results demonstrate safety, tolerability and efficacy of herbal combinations of four plants that seem to act differently but synergistically to regulate glucose-homeostasis.

scholarly journals PHOSPHATIDYLINOSITOL -3KINASE (PI3K) DI PERBENIHAN ADIPOSIT YANG DIPAJAN GLUKOSA TINGGI DENGAN RETINOL

2018 ◽  
Vol 22 (2) ◽  
pp. 109
Author(s):  
Novi Khila Firani ◽  
Bambang Prijadi
Keyword(s):  
High Glucose ◽  
Glucose Transporter ◽  
Determination Method ◽  
Glucose Transporter 4 ◽  
Phosphatidylinositol 3 Kinase ◽  
Elisa Method ◽  
Glucose Levels ◽  
Glucose Exposure ◽  
The Mean

Retinol is one of the active forms of vitamin A. In the previous study, it was known that retinol level in serum of DM patient waslower than in healthy people, which correlated with an increase of the glucose levels in these patients. The importance of retinol in insulinsignaling mechanisms that play a role in the pathogenesis of DM is still unknown. One of the components that play a role in insulinsignaling on adipocytes is phosphatidylinositol-3 kinase (PI3K), which encourages the translocation of glucose transporter-4 (GLUT4) tothe cell surface. The aim of this study was to know the importance of retinol therapy in the levels of PI3K enzyme on visceral adipocyteculture with high glucose exposure (25 mM) as a model of DM in vitro by determination method. Retinol therapy was given at a doseof 0.1 μM, 1 μM , and 10 μM. Measurement of PI3K level was done by ELISA method. The mean (SD) levels of PI3K enzyme were 1.91(0.27), 0.94 (0.15), 1.98 (0.22), 1.69 (0.81), 2.04 (0.16) ng/mL respectively, for adipocyte cultures exposed to 5mM glucose (as aphysiological condition), 25mM glucose, and 25mM glucose concentration with doses of retinol therapy 0.1 μM, 1 μM and10 μM. Theresults of this study indicated that high glucose exposure (25 mM) decreased the level of PI3K compared with adipocyte’s culture on5 mM glucose exposure. Retinol therapy with a dose of 0.1μM, 1μM and10 μM on adipocyte culture exposed with high glucose couldincrease the levels of PI3K.

Possible role of blood insulin levels on glutathione S-transferase activities from different tissues of male rats

1990 ◽  
Vol 68 (2) ◽  
pp. 170-173 ◽  
Author(s):  
Cristina E. Carnovale ◽  
Juan A. Monti ◽  
Viviana A. Catania ◽  
Maria C. Carrillo
Keyword(s):  
Diabetic Rats ◽  
Male Rats ◽  
Blood Levels ◽  
Transferase Activity ◽  
Glutathione S Transferase ◽  
Insulin Levels ◽  
Blood Insulin ◽  
Glucose Levels

The activity of in vitro glutathione S-transferase towards 1-chloro-2,4-dinitrobenzene was examined in liver, renal cortex, and small intestine (duodenum, jejunum, ileum) after the in vivo treatment of male Wistar rats with streptozotocin or alloxan. The studies were performed at 2, 10, 24, and 48 h and 7 and 15 days after streptozotocin treatment or 24 and 48 h after alloxan treatment. The results indicated that while the blood levels of insulin–glucose did not show variations, there were no alterations of the glutathione S-transferase activity in the tissues tested. On the other hand, when the treatments caused modifications on blood insulin–glucose levels, there were changes of glutathione S-transferase activity in all tissues (except in the ileum) in such a way that a direct relationship between plasma insulin levels and glutathione S-transferase activity could be demonstrated. These results were also confirmed through insulin administration to control and diabetic rats. The data demonstrate a possible regulation of glutathione S-transferase activity by blood insulin and (or) glucose levels in the tissues tested.Key words: insulin, glutathione S-transferase, streptozotocin, alloxan.

Myocardial metabolic effects of in vivo hydralazine treatment of streptozotocin-diabetic rats

1991 ◽  
Vol 260 (2) ◽  
pp. H516-H521
Author(s):  
A. H. Burns ◽  
L. A. Burns ◽  
L. U. Jurenka ◽  
W. R. Summer
Keyword(s):  
Glucose Oxidation ◽  
Mechanical Response ◽  
Treated Group ◽  
Diabetic Rats ◽  
Metabolic Effects ◽  
Mechanical Function ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Streptozotocin Diabetic Rats

We determined myocardial pumping capacity, glucose oxidation, and mechanical response to ischemia in streptozotocin-diabetic rats treated for 4 wk with or without hydralazine (0.5 mg/g of chow). Plasma triglycerides and cholesterol were decreased 73 and 50%, respectively, in the treated animals. Blood glucose levels were greater than 400 mg/100 g in both groups. Hearts were perfused in the working configuration with buffer containing 5 mM [U-14C]glucose. Starling curves were constructed by increasing left atrial filling pressure from 5 to 20 cm of water. Diabetic heart mechanical function was depressed compared with control and hydralazine treatment restored function to normal. Oxidation of [U-14C]glucose was comparably depressed in the treated and untreated diabetics. The provision of 1 mM dichloroacetate in the perfusate increased glucose oxidation in the hearts from hydralazine-treated rats, however. Twenty minutes of global ischemia resulted in 65% decrease in mechanical function in the hearts of hydralazine-treated group vs. 15% for hearts from nontreated diabetics. The data suggest that measures to normalize lipid metabolism may not normalize myocardial glucose oxidation or permit better mechanical recovery after ischemia in the diabetic myocardium.

In Vitro and In Vivo Profiles and Characterization of Insulin Nanocarriers Based in Flexible Liposomes Designed for Oral Administration

2019 ◽  
Vol 16 (8) ◽  
pp. 948-960
Author(s):  
Sara Melisa Arciniegas Ruiz ◽  
María Josefa Bernad Bernad ◽  
Raquel Lopez Arellano ◽  
Roberto Diaz Torres ◽  
Sara Del Carmen Caballero Chacón ◽  
...  
Keyword(s):  
Polyacrylamide Gel Electrophoresis ◽  
Oral Route ◽  
Diabetic Rats ◽  
Release Profile ◽  
Therapeutic Effects ◽  
Subcutaneous Route ◽  
In Vivo Test ◽  
Glucose Levels

Background: Alternatives routes of delivery for Insulin have been evaluated to improve treatment for Diabetes Mellitus. The oral route is the most convenient physiologically; it releases in a similar way to endogenous secretion. Flexible liposomes have deformable abilities to pass through membranes with adequate therapeutic effects, but they have been tested only dermally. Objective: Our aim was to develop an oral nanocarrier based on flexible liposomes for insulin with polymer addition to reduce gastrointestinal degradation. Methods: Different percentages of polyethylene glycol were added to a conventional formulation of flexible liposomes. The manufacturing procedure was the heating method. Z potential, size particle, polydispersity index and encapsulation percentage were evaluated. A release profile was performed in the stomach and intestinal pH mediums by two-stage reverse dialysis method. The in-vivo test was performed in experimental diabetic rats by oral, transdermal and subcutaneous routes. Results: All the formulations showed polydispersity but adequate Z potential. The 10% PEG formulation obtained the best insulin enclosure with 81.9%. The insulin integrity after preparation was confirmed by polyacrylamide gel electrophoresis. PEG and non-PEG formulations showed similar behavior in acid release profile but the release and stability of lipid structures were better and longer in intestinal pH conditions. In vivo tests showed a reduction to normal glucose levels only in subcutaneous route. Conclusion: The polymer inclusion in flexible liposomes generates an adequate nanocarrier for proteins in terms of stability and composition; although its in-vivo use reduces glucose levels in subcutaneous route, the effect was not adequate in oral route.

scholarly journals Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo

2015 ◽  
Vol 35 (4) ◽  
pp. 1425-1436 ◽  
Author(s):  
Tingfang Chen ◽  
Li Yang Zheng ◽  
Wenzhen Xiao ◽  
Dingkun Gui ◽  
Xiaoxia Wang ◽  
...  
Keyword(s):  
High Glucose ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Option ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Mesenchymal Transition ◽  
Epithelial Marker

Background: Epithelial-to-mesenchymal transition (EMT) is a potential pathway leading to podocyte depletion and proteinuria in diabetic kidney disease (DKD). Here, we investigated the protective effects of Emodin (EMO) on high glucose (HG) induced-podocyte EMT in-vitro and in-vivo. Methods: Conditionally immortalized mouse podocytes were exposed to HG with 30μg /ml of EMO and 1μmol/ml of integrin-linked kinase (ILK) inhibitor QLT0267 for 24 h. Streptozotocin (STZ)-induced diabetic rats were treated with EMO at 20 mg· kg-1· d-1 and QLT0267 at 10 mg· kg-1· w-1 p.o., for 12 weeks. Albuminuria and blood glucose level were measured. Immunohistochemistry, immunofluorescence, western blotting and real-time PCR were used to detect expression of ILK, the epithelial marker of nephrin and the mesenchymal marker of desmin in-vitro and in-vivo. Results: HG increased podocyte ILK and desmin expression while decreased nephrin expression. However, EMO significantly inhibited ILK and desmin expression and partially restored nephrin expression in HG-stimulated podocytes. These in-vitro observations were further confirmed in-vivo. Treatment with EMO for 12 weeks attenuated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. EMO also repressed renal ILK and desmin expression, preserved nephrin expression, as well as ameliorated albuminuria in STZ-induced diabetic rats. Conclusion: EMO ameliorated glucose-induced EMT and subsequent podocyte dysfunction partly through ILK and desmin inhibition as well as nephrin upregulatiotion, which might provide a potential novel therapeutic option for DKD.

scholarly journals Decrease of Klotho in the Kidney of Streptozotocin-Induced Diabetic Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Meng-Fu Cheng ◽  
Li-Jen Chen ◽  
Juei-Tang Cheng
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Diabetic Rats ◽  
Glucose Levels ◽  
Renal Functions ◽  
Blood Glucose Levels ◽  
Convoluted Tubules ◽  
The Brain ◽  
Darby Canine Kidney

Theklothogene is expressed in a limited number of tissues, most notably in distal convoluted tubules in the kidney and choroid plexus in the brain. A previous study suggested that Klotho increases resistance to oxidative stress. However, changes of Klotho expression in high glucose-induced oxidative stress remain unclear. In the present study, we used streptozotocin-induced diabetic rats (STZ rats) to examine the effects of insulin, phloridzin or antioxidant, tiron on diabetic nephropathy. Both insulin and phloridzin reversed the lower Klotho expression levels in kidneys of STZ rats by the correction of hyperglycemia. Also, renal functions were improved by these treatments. In addition to the improvement of renal functions, the decrease of Klotho expression in kidney of STZ rats was also reversed by tiron without changing blood glucose levels. The reduction of oxidative stress induced by high glucose can be considered for this action of tiron. This view was further confirmed in vitro using high glucose-exposed Madin-Darby canine kidney (MDCK) epithelial cells. Thus, we suggest that decrease of oxidative stress is not only responsible for the improvement of renal function but also for the recovery of Klotho expression in kidney of STZ rats.

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