Enhanced expression of group IIA secreted phospholipase A2 by elevated glucose levels in cytokine-stimulated rat mesangial cells and in kidneys of diabetic rats

2005 ◽  
Vol 63 (05) ◽  
pp. 356-367 ◽  
Author(s):  
G.J. Vlachojannis ◽  
K. Scholz-Pedretti ◽  
W. Fierlbeck ◽  
H. Geiger ◽  
J. Pfeilschifter ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Mesangial Cells ◽  
Diabetic Rats ◽  
Glucose Levels ◽  
Secreted Phospholipase A2 ◽  
Enhanced Expression ◽  
Elevated Glucose

scholarly journals Leeches alleviates diabetic macroangiopathy by increasing nitric oxide production in rat aorta and restoring endothelium-dependent vasodilatation

2021 ◽  
Author(s):  
Zhaohui Fang ◽  
Xiu Hu ◽  
Zhi Chen ◽  
Jing Xie ◽  
Di Wu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Glucose ◽  
High Glucose ◽  
Mesangial Cells ◽  
Rat Aorta ◽  
Diabetic Rats ◽  
No Production ◽  
Active Components ◽  
Glucose Levels ◽  
Diabetic Macroangiopathy

IntroductionDiabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose level over a prolonged period, leading to severe damage in tissues including the heart, blood vessels, eyes and the kidneys. Danzhi Jiangtang Capsule (DJC) is an effective drug for diabetes, but the mechanism responsible for its efficacy remains unknown. This study aimed to explore the effective ingredient of DJC that ameliorated diabetes and the possible mechanisms.Material and methodsWe orally treated streptozotocin (STZ)-induced diabetic rats with 540 mg/kg DIC or the same dose of its four active components, namely Leeches, Pseudostellaria Polysaccharides (PP), Paeonia Suffruticosa Andr (PSA) and Rehmannia Glutinosa Libosch (RGL), respectively for 8 weeks.ResultsAlthough all of these components could reduce blood glucose levels in diabetic rats, the extent of alleviation of DJC was more pronounced than all of its four ingredients. Unlike the other three components, Leeches is the only effective ingredient of DJC that decreased tetrahydrobiopterin (BH4) oxidation to activate endothelial nitric oxide synthase (eNOS), and increased nitric oxide (NO) production, leading to improved endothelium-dependent relaxation both in diabetic rats and in immortalized human mesangial cells under the stimulation of high glucose.ConclusionsLeeches could alleviate diabetic macroangiopathy by inhibiting NO release in endothelial cells under high-glucose condition.

scholarly journals Stimulation of Fibronectin Matrix Assembly by Lysine Acetylation

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 655 ◽  
Author(s):  
Maria E. Vega ◽  
Birgit Kastberger ◽  
Bernhard Wehrle-Haller ◽  
Jean E. Schwarzbauer
Keyword(s):  
Mesangial Cells ◽  
Matrix Effects ◽  
Binding Activity ◽  
Lysine Acetylation ◽  
Matrix Assembly ◽  
Cell Contractility ◽  
Glucose Levels ◽  
The Matrix ◽  
Filtration Apparatus ◽  
Elevated Glucose

Diabetic nephropathy, a devastating consequence of diabetes mellitus, is characterized by the accumulation of extracellular matrix (ECM) that disrupts the kidney’s filtration apparatus. Elevated glucose levels increase the deposition of a fibronectin (FN) matrix by mesangial cells, the primary matrix-producing cells of the kidney, and also increase acetyl-CoA leading to higher levels of lysine acetylation. Here, we investigated the connection between acetylation and the ECM and show that treatment of mesangial cells with deacetylase inhibitors increases both acetylation and FN matrix assembly compared to untreated cells. The matrix effects were linked to lysine 794 (K794) in the β1 integrin cytoplasmic domain based on studies of cells expressing acetylated (K794Q) and non-acetylated (K794R) mimetics. β1(K794Q) cells assembled significantly more FN matrix than wildtype β1 cells, while the non-acetylated β1(K794R) form was inactive. We show that mutation of K794 affects FN assembly by stimulating integrin-FN binding activity and cell contractility. Wildtype and β1(K794Q) cells but not β1(K794R) cells further increased their FN matrix when stimulated with deacetylase inhibitors indicating that increased acetylation on other proteins is required for maximum FN assembly. Thus, lysine acetylation provides a mechanism for glucose-induced fibrosis by up-regulation of FN matrix assembly.

scholarly journals Effect of Elevated Glucose on Endothelin-Induced Store-Operated and Non-Store-Operated Calcium Influx in Renal Mesangial Cells

2000 ◽  
Vol 11 (7) ◽  
pp. 1225-1235
Author(s):  
LETA K. NUTT ◽  
ROGER G. O'NEIL
Keyword(s):  
Calcium Signaling ◽  
High Glucose ◽  
Mesangial Cells ◽  
Calcium Influx ◽  
Calcium Entry ◽  
Calcium Signal ◽  
Glomerular Mesangial Cells ◽  
Glucose Levels ◽  
Elevated Glucose ◽  
Acute And Chronic Exposure

Abstract. Early diabetic nephropathy exhibits renal glomerular hyperfiltration and an increase in renal plasma flow. The hyperfiltration is a dysfunctional state that may arise from a hyperglycemic-induced hypocontractility of glomerular mesangial cells that may be associated with depressed Ca2+signaling events. The present study was designed to determine the effects of acute (minutes) and chronic (days) elevated glucose levels on endothelin-induced calcium signaling with a particular emphasis on the potential influence on stores and store-operated Ca2+influx (SOCI ; also called capacitative calcium entry) in glomerular mesangial cells. Primary cultures of rat mesangial cells were grown in either high (30 mM) or normal (5 mM) glucose-containing media and tested in the presence of either high (30 mM) or normal (5 mM) glucose levels. Intracellular calcium levels were monitored with the calcium-sensitive fluorophore fura-2 before and after treatment with either endothelin-1 (10 nM), to induce typical Ca2+signals, or the endoplasmic reticulum (ER) Ca-ATPase inhibitor thapsagargin (1 μM), to unload ER Ca2+stores. Both acute and chronic exposure to high glucose levels depressed the endothelin-induced calcium signal. However, neither release of Ca2+from stores nor SOCI were depressed by high glucose levels. In contrast, an endothelin-induced calcium entry pathway (likely receptor-operated calcium influx), separate from SOCI, was markedly depressed in the presence of both acute and chronic high glucose levels. The depressant effect of high glucose was rapidly (minutes) reversible upon returning to normal glucose levels. It is concluded that high glucose levels depress endothelin-induced calcium signaling in rat mesangial cells by inhibiting non-SOCI Ca2+entry pathways, namely the receptor-operated Ca2+influx pathway. The glucose-induced alterations in the receptor-operated calcium influx pathway may, in part, contribute to the depressed contractile state of glomerular cells during periods of hyperglycemia.

scholarly journals Trigonelline regulates Wnt/β-catenin signaling in glomerular mesangial cells under high glucose conditions

2021 ◽  
Author(s):  
Chen Chen ◽  
Yan Shi ◽  
Zhen Chen ◽  
Xiangjun Li ◽  
Bo Sun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
High Glucose ◽  
Cell Cycle Progression ◽  
Cell Injury ◽  
Mesangial Cells ◽  
Animal Experiments ◽  
Glomerular Mesangial Cells ◽  
Glucose Levels ◽  
Elevated Glucose

Abstract Background: Trigonelline have hypoglycemic effects. In previous animal experiments, we observed that trigonelline (TRL) treat-ment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced rats, TRL treatment reduced albuminuria, lowered blood sugar, improved renal function and alleviated the pathological alterations within the glomerulus. Methods: We stimulated human mesangial cells (HMC) with high glucose (30 mmol / L) medium. HMCs were transfected with β-catenin plasmid or siRNA to investigate the effect of trigonelline on high glucose-induced excessive proliferation and apoptosis of HMCs, and to understand its mechanism of action. Cell viability was measured by MTT assay. Flow cytometry was used to detect the cell cycle. Cell apoptosis was evaluated by flow cytometry and terminal dUTP transferase nick end labeling (TUNEL) assay. Protein and mRNA expression of β-catenin, Wnt5a, TCF4, Cyclin D1, and CDK4 were detected by western blotting and RT-PCR, respectively. Results: Trigonelline inhibited cell proliferation by blocking cell-cycle progression at the G1 phase and decreased apoptosis via the Wnt/β-catenin pathway. Elevated glucose levels enhanced the expression of β-catenin, an important modulator of diabetic nephropathy, while trigonelline restored up-regulation. Conclusions: High glucose and high expression of β-catenin could lead to cell injury; however, this effect was mitigated by trigonelline via managing the canonical Wnt/β-catenin signaling pathway.

Correlation of diacylglycerol level and protein kinase C activity in rat retina to retinal circulation

1993 ◽  
Vol 265 (5) ◽  
pp. E783-E793 ◽  
Author(s):  
T. Shiba ◽  
T. Inoguchi ◽  
J. R. Sportsman ◽  
W. F. Heath ◽  
S. Bursell ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Diabetic Rats ◽  
Vascular Cells ◽  
Rat Retina ◽  
Glucose Levels ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Elevated Glucose ◽  
Specific Activities

The increases in diacylglycerol (DAG) level and protein kinase C (PKC) activity have been characterized biochemically and functionally in the retina and the brain of diabetic rats as well as in cultured vascular cells. PKC specific activities were increased in the membraneous fraction of retina from streptozotocin (STZ)-induced diabetic rats and the genetically determined diabetic BB rats, respectively, after 1 or 2 wk of diabetes, compared with control. The ratio of total PKC activities from membraneous and cytosol fractions was also increased in the retina of diabetic rats. With diabetes, all the isoenzymes and the total DAG level were increased in the rat retina, whereas no changes were found in the rat brain. Insulin treatment normalized plasma glucose levels and partially prevented the increases in the membraneous PKC activity and all the isoenzymes in the retina. In the retinal endothelial cells, the total DAG level and PKC specific activities are increased by 36 and 22%, respectively, in the membraneous pool when the glucose levels are changed from 5.5 to 22 mM. Activation of PKC activity and isoform beta II by the vitreal injection of phorbol dibutyrate mimicked the abnormal retinal blood circulation observed in diabetic rats (2.22 +/- 0.24 vs. 1.83 +/- 0.40 s). Thus diabetes and elevated glucose levels will increase DAG level and PKC activities and its isoenzyme specifically in vascular cells and may affect retinal hemodynamics.

Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones

2019 ◽  
Vol 89 (1-2) ◽  
pp. 45-54
Author(s):  
Akemi Suzuki ◽  
André Manoel Correia-Santos ◽  
Gabriela Câmara Vicente ◽  
Luiz Guillermo Coca Velarde ◽  
Gilson Teles Boaventura
Keyword(s):  
Thyroid Hormones ◽  
High Fat Diet ◽  
Female Offspring ◽  
Flaxseed Oil ◽  
Diabetic Rats ◽  
High Fat ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Flaxseed Flour ◽  
Maternal Consumption

Abstract. Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (−31%), HFG (−33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (−10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.

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