scholarly journals Diabetic Pathophysiology Enhances Inflammation during Extracorporeal Membrane Oxygenation in a Rat Model

Membranes ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 283
Author(s):  
Yutaka Fujii ◽  
Takuya Abe ◽  
Kikuo Ikegami

Systemic inflammatory responses in patients undergoing extracorporeal membrane oxygenation (ECMO) contribute significantly to ECMO-associated morbidity and mortality. In recent years, the number of type 2 diabetes mellitus patients has increased, and the number of these patients undergoing ECMO has also increased. Type 2 diabetes mellitus is a high-risk factor for complications during ECMO. We studied the effects of ECMO on inflammatory response in a diabetic rat ECMO model. Twenty-eight rats were divided into 4 groups: normal SHAM group (normal rats: n = 7), diabetic SHAM group (diabetic rats: n = 7), normal ECMO group (normal rats: n = 7), and diabetic ECMO group (diabetic rats: n = 7). We measured the plasma levels of cytokines, tumor necrosis factor-α, and interleukin-6. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine (Cr), and liver-type fatty acid binding protein (L-FABP) were examined in the rat cardiopulmonary bypass model to ascertain organ damage. In addition, the lung wet-to-dry weight (W/D) ratio was measured as an index of pulmonary tissue edema. A pathologic evaluation of kidneys was conducted by hematoxylin-eosin (HE) and periodic-acid-methenamine-silver (PAM) staining. In the diabetic ECMO group, levels of cytokines, AST, ALT, LDH, and L-FABP increased significantly, reaching a maximum at the end of ECMO in comparison with other groups (p < 0.05). In addition, hematoxylin-eosin and periodic acid-methenamine-silver staining of renal tissues showed marked injury in the ECMO group (normal ECMO and diabetic ECMO groups). Furthermore, when the normal ECMO and diabetic ECMO groups were compared, severe organ injury was seen in the diabetic ECMO group. There was remarkable organ injury in the diabetic ECMO group. These data demonstrate that diabetes enhances proinflammatory cytokine release, renal damage, and pulmonary edema during ECMO in an animal model.

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199759
Author(s):  
Jiajia Tian ◽  
Yanyan Zhao ◽  
Lingling Wang ◽  
Lin Li

Aims To analyze expression of members of the Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling pathway in the heart and liver in a rat model of type 2 diabetes mellitus (T2DM). Our overall goal was to understand the underlying pathophysiological mechanisms. Methods We measured fasting blood glucose (FBG) and insulin (FINS) in a rat model of T2DM. Expression of members of the TLR4/MyD88/NF-κB signaling pathway as well as downstream cytokines was investigated. Levels of mRNA and protein were assessed using quantitative real-time polymerase chain reaction and western blotting, respectively. Protein content of tissue homogenates was assessed using enzyme-linked immunosorbent assays. Results Diabetic rats had lower body weights, higher FBG, higher FINS, and higher intraperitoneal glucose tolerance than normal rats. In addition, biochemical indicators related to heart and liver function were elevated in diabetic rats compared with normal rats. TLR4 and MyD88 were involved in the occurrence of T2DM as well as T2DM-related heart and liver complications. TLR4 caused T2DM-related heart and liver complications through activation of NF-κB. Conclusions TLR4/MyD88/NF-κB signaling induces production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, leading to the heart- and liver-related complications of T2DM.


2020 ◽  
Author(s):  
Wenhao Song ◽  
Yao Gong ◽  
Pei Tu ◽  
Lin Zhang ◽  
Zhili Jin ◽  
...  

Abstract Background The aim of this study was to analyze the expressions of long noncoding RNA(lncRNA) in rat with type 2 diabetes mellitus(T2DM) complicated with acute myocardial ischemia reperfusion injury(IRI). Methods Type 2 diabetic rats were induced by high calorie diet combined with streptozotocin. IRI rats models were established by the ligation and release of left anterior descending coronary artery(LAD). The expression levels of lncRNA and mRNA in myocardial tissues of rats were detected via high-throughput sequencing technology, and Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Result Transcriptome analyses were performed to show expression profiles of mRNAs and lncRNAs in myocardial tissues of diabetic rats with IRI. A total of 2,476 lncRNAs and 710 mRNAs were differentially expressed between operation group and sham operation group. Then, an mRNA-lncRNA coexpression network was constructed. Finally, the present study verified that TCONS_00036439、TCONS_00151548、TCONS_00153276、TCONS_00344188、TCONS_00277692、TCONS_00236469、TCONS_00236468、TCONS_00153290、TCONS_00360941、TCONS_00142622 were associated with the initiation and development of ischemia reperfusion injury. Then, an lncRNA-mRNA coexpression network was constructed. Conclusion There is differential expression of lncRNAs in myocardial IRI tissues of diabetic rats. Building gene regulation networks to find the nodal gene and lncRNA is useful for understanding the pathogenesis of type 2 diabetes mellitus complicated with acute myocardial ischemia reperfusion injury and providing new therapy target.


2016 ◽  
Vol 29 (suppl 1) ◽  
pp. 3-7 ◽  
Author(s):  
Cacio Ricardo WIETZYCOSKI ◽  
João Caetano Dallegrave MARCHESINI ◽  
Sultan AL-THEMYAT ◽  
Fabiola Shons MEYER ◽  
Manoel Roberto Maciel TRINDADE

ABSTRACT Background: Type 2 Diabetes Mellitus is a multifactorial syndrome with severe complications. Oxidative stress is accepted as a causal factor of chronic complications Aim: To demonstrate alterations in oxidative stress after metabolic surgery. Methods: Twenty-four 2-day-old Wistar rats were used. In 16, Type 2 Diabetes Mellitus was induced by 100 mg/kg streptozotocin injection. The development of diabetes was confirmed after 10 weeks using an oral glucose tolerance test. Eight diabetic rats composed the diabetic surgical group; the remaining eight composed the diabetic group. Eight animals in which diabetes was not induced formed the clinical control group. The Marchesini technique was used in the diabetic surgical group. After 90 days, the rats were sacrificed, and the oxidative stress markers were measured. Results: Thiobarbituric acid reactive substances, superoxide dismutase and catalase were significantly reduced in the diabetic surgical group compared to the diabetic group. Conclusion: The duodenojejunostomy was effective in controlling the exacerbated oxidative stress present in diabetic rats.


2020 ◽  
Author(s):  
Ahmad Gholami ◽  
Mohammad Hossein Dabbaghmanesh ◽  
Younes Ghasemi ◽  
Pedram Talezadeh ◽  
Farhad Koohpeyma ◽  
...  

Abstract Background Pioglitazone as a PPAR-g agonist are used for management of type 2 diabetes mellitus. Nevertheless, evidence showed that the therapeutic modulation of PPARg activity using Pioglitazone may be linked with bone mass reduction and fracture risk in type 2 diabetes mellitus patients. The objective of the current research was to inspect the preventive role of some types of probiotic strains including ( Lactobacillus acidophilus , Lactobacillus reuteri , Lactobacillus casei , Bifidiobacterum longum and Bacillus coagulans ) against pioglitazone-induced bone loss. Methods Streptozotocin (60 mg/kg) was administered for diabetes induction. Diabetic rats were fed orally with pioglitazone (300 mg/kg) and probiotics (1×109 CFU/ml/day) alone and in combination of both for 4 weeks. Dual energy X-ray absorptiometry (DEXA) were used to asses BMD, BMC and area of the femur, spine and tibia at the experiment termination. Serum glucose, serum calcium, alkaline phosphatase, phosphorus, BUN, Creatinine, and urine calcium were also analyzed. Results Administration of pioglitazone and probiotics alone and in combination significantly improved elevated blood glucose. Pioglitazone treatment significantly increased urinary calcium and BUN, and decreased ALP and creatinine. Co-treatment of probiotics with pioglitazone significantly decreased urinary calcium, creatinine and ALP. Pioglitazone showed detrimental effects on femur-BMD whereas treatment with probiotics remarkably ameliorated these effects. Among the tested probiotics Bifidiobacterum longum displayed the best protective effects on pioglitazone-induced bone loss in diabetic rats. Conclusion This study suggests probiotic supplementation in diabetic patients on pioglitazone regime could be considering as a good strategy to ameliorate bone loss induced by pioglitazone.


Author(s):  
Ginpreet Kaur ◽  
Mihir Invally ◽  
Meena Chintamaneni

Abstract: Curcumin is a nutraceutical obtained from the rhizomes of: The present study was targeted to explore the antidiabetic potential of combinatorial extract of curcumin with piperine and quercetin (CPQ) in streptozotocin- and nicotinamide-induced diabetic rats. Diabetes mellitus was induced by single intraperitoneal injection of streptozotocin (55 mg/kg) and nicotinamide (120 mg/kg: Oral administration of CPQ at the dose of 100 mg kg: Treatment with combinatorial extract of curcumin presented a significantly better therapeutic potential when compared with curcumin alone, which reveals that CPQ, with reduced dose of curcumin may serve as a therapeutic agent in the treatment of type 2 diabetes mellitus.


Endocrinology ◽  
2014 ◽  
Vol 155 (4) ◽  
pp. 1197-1206 ◽  
Author(s):  
Christine Hamann ◽  
Ann-Kristin Picke ◽  
Graeme M. Campbell ◽  
Mariya Balyura ◽  
Martina Rauner ◽  
...  

Type 2 diabetes mellitus (T2DM) is associated with increased skeletal fragility and impaired fracture healing. Intermittent PTH therapy increases bone strength; however, its skeletal and metabolic effects in diabetes are unclear. We assessed whether PTH improves skeletal and metabolic function in rats with T2DM. Subcritical femoral defects were created in diabetic fa/fa and nondiabetic +/+ Zucker Diabetic Fatty (ZDF) rats and internally stabilized. Vehicle or 75 μg/kg/d PTH(1–84) was sc administered over 12 weeks. Skeletal effects were evaluated by μCT, biomechanical testing, histomorphometry, and biochemical markers, and defect regeneration was analyzed by μCT. Glucose homeostasis was assessed using glucose tolerance testing and pancreas histology. In diabetic rats, bone mass was significantly lower in the distal femur and vertebrae, respectively, and increased after PTH treatment by up to 23% in nondiabetic and up to 18% in diabetic rats (P &lt; .0001). Diabetic rats showed 23% lower ultimate strength at the spine (P &lt; .0005), which was increased by PTH by 36% in normal and by 16% in diabetic rats (P &lt; .05). PTH increased the bone formation rate by 3-fold in normal and by 2-fold in diabetic rats and improved defect regeneration in normal and diabetic rats (P &lt; .01). PTH did not affect serum levels of undercarboxylated osteocalcin, glucose tolerance, and islet morphology. PTH partially reversed the adverse skeletal effects of T2DM on bone mass, bone strength, and bone defect repair in rats but did not affect energy metabolism. The positive skeletal effects were generally more pronounced in normal compared with diabetic rats.


2021 ◽  
Vol 77 (3) ◽  
pp. 105-110
Author(s):  
Olha Ivanova

Introduction. Type 2 diabetes mellitus (T2DM) increases the risk for atherosclerotic cardiovascular disease and other cardiovascular complications such as cardiac arrhythmias, heart failure, and thrombotic events. Quercetin (Q) possesses a wide range of multiple activities: anti-diabetic, anti-proliferative, anti-atherosclerotic, antioxidant, anti-inflammatory, anti-thrombotic, anti-apoptotic effects and is regarded as a candidate for the role of cardiovascular complications protecting agent. The aim of this study was to assess the effects of Q on the functional state of cardiovascular system and haemostasis in diabetic rats. Materials and Methods. T2DM was induced in Wistar rats by a high-caloric diet during 14 weeks combined with intraperitoneal injections of 25 mg/kg streptozotocin twice per week. All diabetic animals were divided into three groups: treated with solvent and with Q (in dose 10 and 50 mg/kg/day per os) for 8 weeks after diabetes induction. Fibrinogen concentration and induced euglobulin fibrinolysis time were measured in plasma using reagent kits. Electrocardiograms were recorded in leads II. Results. It was established that Q in dose 50 mg/kg b.w. prevents in the formation of sinus tachycardia in experimental animals. In addition, Q in both doses inhibits the development of myocardial diastolic dysfunction, which was confirmed by prolongation of T-P interval and a decrease of duration of the T wave in comparison with diabetic rats. Q in both doses restorated the processes of coagulations and fibrinolysis, as indicated by a decrease of fibrinogen levels and the time of thrombolysis compared to diabetic rats. Conclusions. Q, independently of dose, inhibits the development of myocardial diastolic dysfunction and reduces prothrombotic potential in rats with type 2 diabetes, which may ameliorate diabetic cardiovascular risk. This data justify the perspective of Q for the prevention and management of cardiovascular complications in patients with type 2 diabetes.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ni Wayan Desi Bintari ◽  
Putu Ayu Parwati

Type 2 Diabetes Mellitus (T2DM) is the more common type of diabetes results from the ineffective use of insulin. Improvement of the metabolic system in T2DM patients can be done through the regulation of gut microbiota balance. Gut microbial improvement can be modulated directly by probiotic food consumption. Soygurt is probiotic food with a low glycemic index (GI) and glycemic load (GL) value and rich in isoflavones, which has a potential effect in reducing diabetes risk. The aim of this study is to determine the effect of soygurt consumption in blood glucose levels and body weight of albino wistar rats (Rattus norvegitus). Reseach using a completely randomized design for experimental study. Subjects of this research are 30 male rats (R. norvegistus) aged 2-3 months with average body weight 150-200 gr. Diabetic rats were induced by using single intraperitoneal injection (175 mg/kg BW) alloxan monohydrate. Soygurt feeding given once daily using oral gavage feeding. The result showed that soygurt feeding in diabetic rats with three variations of treatment could significantly (p<0,05), lowering blood sugar level and improve body weight after 28 days of treatment. Treatment of 4ml/day soygurt has the highest effect in lowering blood sugar level and improving body weight, followed by treatment of 3ml/day and 2ml/day soygurt.


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