Study of long non-coding RNA and mitochondrial dysfunction in diabetic rats

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Haytham K Kamal ◽  
Amr S Moustafa ◽  
Wael M Elayat ◽  
Noha N Lasheen ◽  
Azza H AbouGhalia
Keyword(s):  
Lipid Profile ◽  
Histological Examination ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Diabetic Heart ◽  
Albino Rats ◽  
Diabetic Kidney

Abstract Diabetes mellitus (DM) is a worldwide health problem. Many factors participate in the pathogenesis of DM, including genetic, autoimmune, metabolic, dietary and environmental factors. Intact mitochondrial function is essential for prompt cellular metabolism and energy balance. Malfunctioning mitochondria lead to disturbed glucose metabolism and therefore evolving of DM. Epigenetics plays a role in the control of geneencoded proteins of mitochondrial function and dynamics. One of the primary epigenetic effectors is a family of long non-coding RNAs. The role of lncRNA, H19 in the regulation of mitochondrial dynamics has been recently investigated. The Aim of the work This study aims to evaluate the possible functional role of lncRNA, H19 and its relation to mitofusin-2 (MFN2) expression in diabetic rats. Subjects and methods This study was performed on adult male albino rats divided into diabetic and control groups. Induction of type 1 DM was conducted through single intraperitoneal injection of streptozotocin. Serum measurement of glucose, lipid profile, urea, creatinine, and creatine kinase were performed. Blood pressure measurement, ECG recording, and echocardiography were also performed. Histological examination of cardiac and renal tissues was also performed. In addition, quantitative expression of cardiac and renal tissue MFN2 and lncRNA H19 was determined using qPCR. Results Serum CK-MB and lipid profile levels were markedly elevated in diabetic group compared to controls. Also, kidney functions (serum creatinine, creatinine clearance and albumin creatinine ratio) were markedly elevated in diabetic group compared to controls. Histological examination revealed necrotic changes and intercellular micro hemorrhages in both cardiac and renal tissues of diabetic rats. Expression level of MFN2 gene was lower in diabetic heart and significantly lower in diabetic kidney, as compared to control. Expression of lncRNA H19 was higher in diabetic heart and diabetic kidney as compared to control but without statistical significance. Conclusion In diabetic rats, hyperglycemia had inverse relationship with mitofusin expression and direct proportional relationship with H19 expression. We concluded that hyperglycemia has effect on mitochondrial dynamics suppressing fusion in favor of fission and mitophagy, while H19 expression serve to counterpart the effect of hyperglycemia. In the future, MFN and H19 could serve as potential therapeutic target to reverse effects of hyperglycemia and its complications in DM.

scholarly journals 20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Tong Zhou ◽  
Lin Sun ◽  
Shuo Yang ◽  
You Lv ◽  
Yue Cao ◽  
...  
Keyword(s):  
Treatment Group ◽  
Kidney Disease ◽  
Cell Apoptosis ◽  
Diabetic Kidney Disease ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Renal Tubular Cell ◽  
Ginsenoside Rg3 ◽  
Diabetic Kidney ◽  
Renal Tubular

20(S)-Ginsenoside Rg3 (20(S)-Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD.

Azuki bean (Vigna angularis) extract reduces oxidative stress and stimulates autophagy in the kidneys of streptozotocin-induced early diabetic rats

2016 ◽  
Vol 94 (12) ◽  
pp. 1298-1303 ◽  
Author(s):  
Shin Sato ◽  
Saori Kataoka ◽  
Akane Kimura ◽  
Yuuka Mukai
Keyword(s):  
Oxidative Stress ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Azuki Bean ◽  
Diabetic Group ◽  
Heme Oxygenase 1 ◽  
Vigna Angularis ◽  
Diabetic Kidney ◽  
Protein Levels ◽  
Sequestosome 1

Diabetic kidney disease is associated with oxidative stress, inflammation, and autophagy. The aim of this study was to investigate the effect of azuki bean (Vigna angularis) extract (ABE) on oxidative stress and autophagy in the kidneys of diabetic rats. Streptozotocin (STZ)-induced diabetic rats received 0, 10, or 40 mg/kg of ABE orally for 4 weeks, whereas vehicle-injected control rats received distilled water. Level of plasma glutathione and expression of heme oxygenase-1 (HO-1), p47phox (NADPH oxidase subunit), and markers associated with autophagy were examined. The glutathione level in the 40 mg/kg ABE-treated diabetic group (ABE-40 group) was higher than that of the untreated diabetic group (ABE-0 group). The HO-1 and p47phox protein expression levels of the ABE-40 group were lower (47% and 33%, respectively) than those of the ABE-0 group. The level of light chain 3B II (LC3B-II) was higher in the ABE-40 group than in the ABE-0 group. Protein levels of p62/sequestosome 1 (p62) in the ABE-40 group were lower than those in the ABE-0 group. Our results suggest that ABE may attenuate STZ-induced diabetic kidney injury by suppressing oxidative stress and (or) by upregulating autophagy.

Protective role of 20-OH ecdysone on lipid profile and tissue fatty acid changes in streptozotocin induced diabetic rats

2013 ◽  
Vol 698 (1-3) ◽  
pp. 489-498 ◽  
Author(s):  
Rajendran Naresh Kumar ◽  
Ramalingam Sundaram ◽  
Palanivelu Shanthi ◽  
Panchanatham Sachdanandam
Keyword(s):  
Fatty Acid ◽  
Lipid Profile ◽  
Protective Role ◽  
Diabetic Rats ◽  
Tissue Fatty Acid

Pharmacotherapy with Thymoquinone Improved Pancreatic β-Cell Integrity and Functional Activity, Enhanced Islets Revascularization, and Alleviated Metabolic and Hepato-Renal Disturbances in Streptozotocin-Induced Diabetes in Rats

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 9-21 ◽  
Author(s):  
Adel Galal El-Shemi ◽  
Osama Adnan Kensara ◽  
Aiman Alsaegh ◽  
Mohammed Hasan Mukhtar
Keyword(s):  
Lipid Profile ◽  
Caspase 3 ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Β Cells ◽  
Insulin Homeostasis

Aims: This study is aimed at evaluating the antidiabetic effects of thymoquinone (TQ) on streptozotocin (STZ)-induced diabetes in rats, and exploring the possible underlying mechanisms. Methods: Diabetes was induced in adult male Wistar rats by intraperitoneal injection of freshly prepared STZ (65 mg/kg). After disease induction, 42 rats were equally assigned to: controls, STZ-diabetic group, and STZ-diabetic group treated with oral TQ (35 mg/kg/day) for 5 weeks. Fasting blood glucose levels were determined weekly, and the animals were euthanized at day 38 post-STZ injection. Blood samples were assessed for glucose-insulin homeostasis parameters (plasma glucose, glycated hemoglobin, serum insulin, homeostatic model assessment of insulin resistance, and insulin sensitivity index) and lipid profile. Resected pancreases were subjected to histological examination and immunohistochemical or enzyme-linked immunosorbent assay assessment to determine the pancreatic expression of insulin sensitizing β-cells, anti-apoptotic protein “survivin,” apoptosis-inducer “caspase-3,” prototypic angiogenic factors (vascular endothelial growth factor [VEGF] and endothelial cluster of differentiation 31 [CD31]), pro- and anti-inflammatory cytokines (interleukin-1beta [IL-1β] and interleukin-10 [IL-10], respectively), thiobarbituric acid reactive substances (TBARS), total glutathione (GSH), and superoxide dismutase (SOD). The hepato-renal statuses were assessed biochemically and histologically. Results: Therapy with TQ markedly improved the integrity of pancreatic islets, glucose-insulin homeostasis-related parameters, lipid profile parameters, and hepato-renal functional and histomorphological statuses that collectively were severely deteriorated in untreated diabetic group. Mechanistically, TQ therapy efficiently increased insulin producing β-cells, upregulated survivin, VEGF, CD31, IL-10, GSH and SOD, and downregulated caspase-3, IL-1β, and TBARSs in the pancreatic tissues of STZ-diabetic rats. Conclusions: These findings prove the anti-diabetic potential of TQ and its efficacy in regenerating pancreatic β-cells and ameliorating pancreatic inflammation and oxidative stress, and highlight its novelty in repressing apoptosis of β-cells and enhancing islet revascularization in STZ-diabetic rats. Further studies are required to support these findings and realize their possible clinical significance.

scholarly journals Effect of Some Indian Herbs on Dyslipidemia in Streptozotocin Induced Diabetic Rats

2018 ◽  
Vol 2 (1) ◽  
pp. 24
Author(s):  
Anu Chandra ◽  
Ravjit Sabharwal ◽  
Ramesh Chander ◽  
Farzana Mahdi ◽  
Abbas Ali Mahdi
Keyword(s):  
Drug Treatment ◽  
Azadirachta Indica ◽  
Allium Sativum ◽  
Lipid Peroxide ◽  
Hdl Cholesterol ◽  
Diabetic Rats ◽  
Momordica Charantia ◽  
Diabetic Group ◽  
Ocimum Sanctum ◽  
Albino Rats

<p><strong>Background:</strong> Diabetes is one of the commonest and serious metabolic disorders. Much of the morbidity and mortality associated with diabetes is primarily attributed to sequelae requelac of microvascular and macrovascular changes, in which diabetic dyslipidemia is one of the many modifiable risk factors for coronary artery disease, stroke and peripheral vascular disease.</p><p><strong>Objectives:</strong> The main aim of this study was to evaluate the hypoglycemic and antidyslipidemic effect of selected Indian plants in streptozotocin induced diabetic rats.</p><p><strong>Material and Methods:</strong> Azadirachta indica and Ocimm sanctum leaves, Allium sativum bulbs and Momordica charantia fruits were collected, identified taxonomically and extract was obtained. Male Albino rats was used and divided into 8 groups, each consisting of 6 animals, one group act as a control. Diabetes in rats was induced with streptozotocin. Blood samples were collected and biochemical analysis was done for blood sugar, lipid peroxide and lipid profile. The diabetic group without drug treatment was compared with the control, and diabetic plus drug-treated groups were compared with the diabetic group without drug treatment. Data were analyzed using Student ‘t’ test.</p><p><strong>Results:</strong> Our results revealed that administration of streptozotocin in rats caused increase in the levels of glucose, lipid peroxides, cholesterol and triglycerides with lessening of the HDL-cholesterol. Treatment with aqueous extracts of Momordica charantia, Allium sativum, Azadirachta indica and Ocimum sanctum not only reduced the level of blood glucose but also caused lowering of total cholesterol and triglycerides following an increase in the level of HDL-cholesterol.</p><p><strong>Conclusion:</strong> We concluded that the herbal plants tested possess both hypoglycemic and antidyslipidemic activities and their use as a therapeutic tool in diabetes related complications encourage further investigation in this field.</p>

scholarly journals Podocyte bioenergetics in the development of diabetic nephropathy: the role of mitochondria

Endocrinology ◽  
2021 ◽  
Author(s):  
Irena Audzeyenka ◽  
Agnieszka Bierżyńska ◽  
Abigail C Lay
Keyword(s):  
Diabetic Nephropathy ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Signalling Pathways ◽  
Cell Type ◽  
Cellular Functions ◽  
Podocyte Injury ◽  
Underlying Pathogenesis ◽  
Novel Therapeutic

Abstract Diabetic Nephropathy (DN) is the leading cause of kidney failure, with an increasing incidence worldwide. Mitochondrial dysfunction is known to occur in DN and has been implicated in the underlying pathogenesis of disease. These complex organelles have an array of important cellular functions and involvement in signalling pathways; and understanding the intricacies of these responses in health, as well as how they are damaged in disease, is likely to highlight novel therapeutic avenues. A key cell type damaged early in DN is the podocyte and increasing studies have focused on investigating the role of mitochondria in podocyte injury. This review will summarise what is known about podocyte mitochondrial dynamics in DN, with a particular focus on bioenergetic pathways, highlighting key studies in this field and potential opportunities to target, enhance or protect podocyte mitochondrial function in the treatment of DN.

scholarly journals Role of Vernonia Amygdalina on Plasma Lipid Profile, Liver and Kidney Enzymes in Rats with Streptozotocin-Induced Diabetes

2020 ◽  
pp. 93-102
Author(s):  
Gabriel Olukayode Ajayi ◽  
Elvis Uchechukwu Obi ◽  
Elizabeth Namesegua Elegbeleye ◽  
Precious Titilayo Obayemi ◽  
Oyindamola Mary Edamisan
Keyword(s):  
Lipid Profile ◽  
Low Density Lipoprotein ◽  
Plasma Lipid ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Lipoprotein Cholesterol ◽  
Vernonia Amygdalina ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes

Diabetes mellitus is a non-communicable disease which has been associated with liver and kidney injuries, and at the same time affects lipid profiles. The aim of this study was to investigate the role of Vernonia amygdalina (VAM) on plasma lipid profile, liver and kidney enzymes in rats with streptozotocin -induced diabetes. Twenty-five male albino wistar rats weighing between 137 and 223 g were randomly grouped into five of five rats per group as follows: control, diabetic, diabetic + metformin (MET), diabetic + VAM at 150, 300 mg/kg. Diabetes was induced by administration of 45 mg/kg body weight streptozotocin (STZ) dissolved in citrate buffer (0.01 M, pH 4.5) by single intraperitoneal injection. Three days after, when diabetes was confirmed, MET and VAM were administered daily by oral gavage for 7 days. Animals were fasted overnight after the last administration of MET and VAM, sacrificed, blood was collected and plasma prepared for lipid profile estimation. Liver and kidney were collected, weighed, homogenized and supernatants obtained for enzymes and biochemical assays. There were no significant (p>0.05) change in the weights of animal, liver and kidney, liver/rat and kidney/rat ratios, plasma cholesterol (CHOL) concentration, activities of liver and kidney aspartate aminotransferase (AST), alanine aminotransferase (ALT), liver gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and liver and kidney total protein (TPRO) concentrations; significant (p<0.05) decrease in triglyceride (TRIG), high density lipoprotein-cholesterol (HDL), low density lipoprotein-cholesterol (LDL), very low density lipoprotein-cholesterol (VLDL); and significant (p<0.05) increase in fasting blood glucose (FBG) level, kidney GGT, LDH activities, liver and kidney creatinine (CREA) and total bilirubin (TBIL) concentrations of diabetic (STZ) rats compared with normal control. The treatment of the diabetic rats with MET and VAM significantly modulated positively these parameters compared with the diabetic rats. This study further explains the protective role played by VAM in dyslipidaemia, liver and kidney injuries resulting from diabetes.

scholarly journals Assessment of Fertility Effect and Hypolipidemic Activity of Carica papaya (Linn) Leaf Methanol Extract in Male Diabetic Rats

2021 ◽  
pp. 58-69
Author(s):  
Opeyemi O. Ayodele ◽  
Ifeoluwa M. Dada ◽  
Rotimi K. Adekunle
Keyword(s):  
Lipid Profile ◽  
Plasma Glucose ◽  
Carica Papaya ◽  
Methanol Extract ◽  
Sperm Count ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Control Group ◽  
Albino Rats ◽  
Spectrophotometric Methods

Aim: Diabetes mellitus (DM) is a prevalent metabolic disorder that leads to other microvascular and macrovascular complications. Diabetes affects fertility and blood clotting, and also cause impaired lipid profile thus leading to increased atherogenic risks and coronary diseases. This research investigates the effects of Carica papaya leaf methanol extract on fertility indices and lipid profile of male diabetic rats. Methodology: Male Wistar albino rats were randomly divided into five groups of six rats each. Diabetes was induced in the rats by a single intraperitoneal injection of streptozotocin (55 mg/kg). Diabetic rats were treated orally with 100 and 200 mg/kg C. papaya methanol extract for 14 days. At the end of administration, the plasma glucose concentration and lipid profile were assayed by spectrophotometric methods; seminal analysis was carried out for evaluation of morphology, motility and sperm count under the microscope. The bleeding and clotting times of the rats were also determined. Results: C. papaya leaf methanol extract caused significant (p = 0.05) reduction in plasma glucose, total cholesterol, triglycerides, VLDL-C, LDL-C, bleeding and clotting times of diabetic treated rats, while the HDL-C of treated groups were significantly (p = 0.05) elevated compared to the diabetic control. Percentage normal cells were lower in diabetic control rats (41.4±4.4%) and C. papaya treated groups (50.0±8.5% for 100 mg/kg; 47.5±9.1% for 200 mg/kg) compared with the normal control group (69.5±5.6%). Similar results were recorded for sperm count. The qualitative phytochemical screening showed the presence of steroids, anthraquinone, tannin, and other bioactive compounds. Conclusion: findings from this study indicated that C. papaya leaf methanol extract could possess hypoglycemic and hypolipidemic activities. Thus, could be considered as a potential source of bio pharmacological agent for management and control of DM and its complications. Prolonged administration of C. papaya leaves may negatively affect male fertility.

scholarly journals The E3 ligase MARCH5 is a PPARγ target gene that regulates mitochondria and metabolism in adipocytes

2019 ◽  
Vol 316 (2) ◽  
pp. E293-E304 ◽  
Author(s):  
Simon T. Bond ◽  
Sarah C. Moody ◽  
Yingying Liu ◽  
Mete Civelek ◽  
Claudio J. Villanueva ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Mouse Strains ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolic Genes ◽  
And Function

Mitochondrial dynamics refers to the constant remodeling of mitochondrial populations by multiple cellular pathways that help maintain mitochondrial health and function. Disruptions in mitochondrial dynamics often lead to mitochondrial dysfunction, which is frequently associated with disease in rodents and humans. Consistent with this, obesity is associated with reduced mitochondrial function in white adipose tissue, partly via alterations in mitochondrial dynamics. Several proteins, including the E3 ubiquitin ligase membrane-associated RING-CH-type finger 5 (MARCH5), are known to regulate mitochondrial dynamics; however, the role of these proteins in adipocytes has been poorly studied. Here, we show that MARCH5 is regulated by peroxisome proliferator-activated receptor-γ (PPARγ) during adipogenesis and is correlated with fat mass across a panel of genetically diverse mouse strains, in ob/ob mice, and in humans. Furthermore, manipulation of MARCH5 expression in vitro and in vivo alters mitochondrial function, affects cellular metabolism, and leads to differential regulation of several metabolic genes. Thus our data demonstrate an association between mitochondrial dynamics and metabolism that defines MARCH5 as a critical link between these interconnected pathways.

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