scholarly journals Induction of Caveolin-3/RyR2 By Liraglutide Ameliorates Diabetic Cardiomyopathy

2021 ◽  
Author(s):  
Xu Li ◽  
Zebin Ni ◽  
Junwu Wang ◽  
Xiuying Ye ◽  
Yujing Shen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Myocardial Dysfunction ◽  
Cardiac Tissues ◽  
No Signaling

Abstract Background Liraglutide (LIRA), a Glucagon-like peptide-1 receptor agonist (GLP-1RA), showed potent cardioprotective effects with the mechanism remained incompletely understood. Caveolin-3 (Cav3) is the cardiomyocytes specific caveolae structural protein, decreased in the diabetic heart. Therefore, this study aimed to investigate whether LIRA exerts its effect on cardiac function in rats with type 2 diabetes mellitus (T2DM) via enhance Cav3 expression. Methods T2DM rats were used as study subjects and randomly divided into four groups: 1) CON group, 2) CON+L group, 3) DM group and 4) DM+L group. All rats received either saline or LIRA 0.2 mg/kg (by i.p injection) per day for 4 weeks. After the model was successfully established, cardiac function was determined by invasive hemodynamic evaluation methods. Immunohistochemistry and western blot were performed to understand the molecular mechanism between cardiac function and LIRA. Results Based on our results, DM group displayed higher blood glucose than Con group (20.57±2.75 mol/L vs. 4.34±0.21 mol/L), while blood glucose level in DM+L group was lower than DM group after received LIRA (10.36±1.84 mol/L). LVSP (91.39±4.98 mmHg), LV +dp/dtmax (4040.74±197.72 mmHg/s) were significantly reduced in DM group, and diabetic rats also exhibited reduced -dp/dtmax (2926.5±142.3 mmHg/s) and elevated LVEDP (10.87±0.83 mmHg). LIRA treatment showed a trend to enhance LVSP (110.76±5.61 mmHg) and ± dp/dtmax (5860.41±200.32 mmHg and 3996.8±179.3 mmHg), decreased LVEDP (7.23±0.58 mmHg). The expression of Cav3, eNOS and RyR2 was significantly decreased in the myocardium in DM group, which increased in DM+L group after LIRA administrated. Hemodynamic data showed DM rats exhibited impairment of myocardial function, while LIRA improved cardiac systolic and diastolic function, attenuate diabetic cardiomyopathy injury by improving Cav3/eNOS/NO signaling, reducing ROS level in cardiac tissues, and increasing interaction of Cav3 and ryanodine receptor 2 (RyR2). Conclusions Liraglutide ameliorates cardiac dysfunction in rats with type 2 diabetes mellitus via reducing ROS level in cardiac tissues, improving Cav3/eNOS/NO signaling and increasing interaction of Cav3 and RyR2. Keywords Type-2 diabetes Mellitus, liraglutide, caveolin-3, ryanodine receptor2, myocardial dysfunction

Epigenetic modulation of autophagy genes linked to diabetic nephropathy by administration of isorhamnetin in Type 2 diabetes mellitus rats

Epigenomics ◽  
2021 ◽  
Author(s):  
Marwa Matboli ◽  
Doaa Ibrahim ◽  
Amany H Hasanin ◽  
Mohamed Kamel Hassan ◽  
Eman K Habib ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Light And Electron Microscopy ◽  
Lipid Profiles ◽  
Mirna Regulation ◽  
Protein Levels

Aim: To assess isorhamnetin efficacy for diabetic kidney disease in a Type 2 diabetes mellitus rat model, through investigating its effect at the epigenetic, mRNA and protein levels. Materials & methods: Type 2 diabetes mellitus was induced in rats by streptozotocin and high-fat diet. Rats were treated with isorhamnetin (50 mg/kg/d) for 4 or 8 weeks. Fasting blood glucose, renal and lipid profiles were evaluated. Renal tissues were examined by light and electron microscopy. Autophagy genes ( FYCO1, ULK, TECPR1 and  WIPI2) and miR-15b, miR-34a and miR-633 were assessed by qRT-PCR, and LC3A/B by immunoblotting. Results: Isorhamnetin improved fasting blood glucose, renal and lipid profiles with increased autophagosomes in renal tissues. It suppressed miRNA regulation of autophagy genes Conclusion: We propose a molecular mechanism for the isorhamnetin renoprotective effect by modulation of autophagy epigenetic regulators.

scholarly journals Application value of combination therapy of periodontal curettage and root planing on moderate-to-severe chronic periodontitis in patients with type 2 diabetes

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Yonghuan Bian ◽  
Changhao Liu ◽  
Zhaojiang Fu
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Chronic Periodontitis ◽  
Root Planing ◽  
Tnf Α ◽  
Significant Difference ◽  
Hs Crp

Abstract Background Our study attempted to observe the value of periodontal curettage combined with root planing on moderate-to-severe chronic periodontitis in patients with type 2 diabetes. Methods There involved 72 patients with type 2 diabetes mellitus complicated with moderate-to-severe chronic periodontitis who were diagnosed and treated in our hospital from January 2019 to December 2019. The patients enrolled were randomly divided into four groups using a computer-generated table: root planing and periodontal curettage combined group (n = 18), root planning group (n = 18), periodontal curettage group (n = 18) and cleansing group (n = 18). Blood glucose, plaque index (PI), gingival index (GI), probing depth (PD), attachment loss (AL), serum levels of inflammatory factors (Tumor Necrosis Factor Alpha [TNF- α] and hypersensitive C-reactive protein [hs-CRP]) were observed before and after treatment. The collecting dates were analyzed by the chi-square χ 2 test, repeated measurement analysis of variance, or t-test according to different data types and research objectives. Results Before treatment, there was no significant difference in PI, GI, PD and AL among the four groups (P> 0.05), while after 3-month treatment, the levels of PI, GI, PD and AL in the combined group were lower than those in the root planing group, periodontal curettage group and cleansing group, with both root planing group and periodontal curettage group significantly lower than cleansing group (P< 0.05). The fasting blood glucose, 2-h postprandial blood glucose and glycosylated hemoglobin in the combined group, root planing group, periodontal curettage group and cleansing group were significantly lower than those before treatment (P < 0.05). Before treatment, there was no significant difference in TNF- α and hs-CRP among the four groups (P> 0.05), but the levels of TNF- α and hs-CRP in the four groups decreased significantly after 3-month treatment (P< 0.05). The levels of TNF- α and hs-CRP in the combined group were lower than those in the root planing group, periodontal curettage group and cleansing group, and those in the root planing group and periodontal curettage group were significantly lower than those in the cleansing group (P< 0.05). Conclusion The combination therapy of periodontal curettage and root planing exerted beneficial effects on moderate-to-severe chronic periodontitis in patients with type 2 diabetes mellitus, which holds the potential to maintain the level of blood glucose and improve the quality of life of the patients.

scholarly journals Pharmaceutical hit of anti type 2 Diabetes mellitus on the phenolic extract of Malaka (Phyllanthus emblica L.) flesh

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Musri Musman ◽  
Mauli Zakia ◽  
Ratu Fazlia Inda Rahmayani ◽  
Erlidawati Erlidawati ◽  
Safrida Safrida
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Blood Glucose ◽  
Phyllanthus Emblica ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Phenolic Extract

Abstract Background Ethnobotany knowledge in a community has shaped local wisdom in utilizing plants to treat diseases, such as the use of Malaka (Phyllanthus emblica) flesh to treat type 2 diabetes. This study presented evidence that the phenolic extract of the Malaka flesh could reduce blood sugar levels in the diabetic induced rats. Methods The phenolic extract of the P. emblica was administrated to the glucose-induced rats of the Wistar strain Rattus norvegicus for 14 days of treatment where the Metformin was used as a positive control. The data generated were analyzed by the two-way ANOVA Software related to the blood glucose level and by SAS Software related to the histopathological studies at a significant 95% confidence. Results The phenolic extract with concentrations of 100 and 200 mg/kg body weight could reduce blood glucose levels in diabetic rats. The post hoc Dunnet test showed that the administration of the extract to the rats with a concentration of 100 mg/kg body weight demonstrated a very significant decrease in blood glucose levels and repaired damaged cells better than administering the extract at a concentration of 200 mg/kg weight body. Conclusion The evidence indicated that the phenolic extract of the Malaka flesh can be utilized as anti type 2 Diabetes mellitus without damaging other organs.

scholarly journals Associations of markers of arterial stiffness and remodeling with new-onset type 2 diabetes mellitus

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
F Ahmadizar ◽  
K Wang ◽  
F Mattace Raso ◽  
MA Ikram ◽  
M Kavousi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Arterial Stiffness ◽  
Wall Stress ◽  
Lipid Lowering ◽  
Circumferential Wall Stress ◽  
Increased Risk

Abstract Funding Acknowledgements Type of funding sources: None. Background. Arterial stiffness/remodeling results in impaired blood flow and, eventually, decreased glucose disposal in peripheral tissues and increased blood glucose. Besides, increased arterial stiffness/remodeling may lead to hypertension, as a potential reciprocal risk factor for type 2 diabetes mellitus (T2D). We, therefore, hypothesized that increased arterial stiffness/remodeling is associated with an increased risk of T2D. Purpose. To study the associations between arterial stiffness/remodeling and incident T2D. Methods. We used the prospective population-based Rotterdam Study. Common carotid arterial properties were ultrasonically determined in plaque-free areas. Aortic stiffness was estimated by carotid-femoral pulse wave velocity (cf_PWV), carotid stiffness was estimated by the carotid distensibility coefficient (carDC). Arterial remodeling was estimated by carotid artery lumen diameter (carDi), carotid intima-media thickness (cIMT), mean circumferential wall stress (CWSmean), and pulsatile circumferential wall stress (CWSpuls). Cox proportional hazard regression analysis was used to estimate the associations between arterial stiffness/remodeling and the risk of incident T2D, adjusted for age, sex, cohort, mean arterial pressure (MAP), antihypertensive medications, heart rate, non- high-density lipoprotein (HDL)-cholesterol, lipid-lowering medications, and smoking. We included interaction terms in the fully adjusted models to study whether any significant associations were modified by sex, age, blood glucose, or MAP. Spearman correlation analyses were applied to examine the correlations between measurements of arterial stiffness/remodeling and glycemic traits. Results. We included 3,055 individuals free of T2D at baseline (mean (SD) age, 67.2 (7.9) years). During a median follow-up of 14.0 years, 395 (12.9%) T2D occurred. After adjustments, higher cf_PWV (hazard ratio (HR),1.18; 95%CI:1.04-1.35), carDi (1.17; 1.04-1.32), cIMT (1.15; 1.01-1.32), and CWSpuls (1.28; 1.12-1.47) were associated with increased risk of incident T2D. After further adjustment for the baseline glucose, the associations attenuated but remained statistically significant. Sex, age, blood glucose, or MAP did not modify the associations between measurements of arterial stiffness/remodeling, and incident T2D. Among the population with prediabetes at baseline (n = 513) compared to the general population, larger cIMT was associated with a greater increase in the risk of T2D. Most measurements of arterial stiffness/remodeling significantly but weakly correlated with baseline glycemic traits, particularly with blood glucose.  Conclusions. Our study suggests that greater arterial stiffness/remodeling is independently associated with an increased risk of T2D development. Blood glucose and hypertension do not seem to play significant roles in these associations. Further studies should disentangle the underlying mechanism that links arterial stiffness/remodeling and T2D.

scholarly journals Oxidative stress in patients with type 2 diabetes mellitus treated with metformin

2017 ◽  
Vol 27 (2) ◽  
pp. 25857
Author(s):  
Samuel Selbach Dries ◽  
Bárbara Da Silveira Soares ◽  
Ana Luiza Ziulkoski ◽  
Simone Gasparin Verza ◽  
Rafael Linden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Superoxide Dismutase ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Side Effects ◽  
Diabetic Complications

*** Oxidative stress in patients with type 2 diabetes mellitus treated with metformin ***AIMS: To evaluate oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin, relating these values to its side effects, plasma levels, glycemic control, diabetic complications, lipid profile, and the influence of pharmacotherapeutic follow-up.METHODS: Patients with type 2 diabetes mellitus, on metformin and in pharmacotherapeutic follow-up for four months, were evaluated. The pharmacotherapeutic follow-up consisted in providing information and answering patients’ questions about medication and disease. In addition, administration times, dosages, and presence or absence of side effects related to the use of metformin were verified. Glycemic and lipid profile, oxidative stress (superoxide dismutase and malondialdehyde) and plasma metformin were evaluated. Pearson’s correlation and Spearman’s correlation were performed to evaluate the relationship between the variables at the beginning of the study. The independent t-test and Mann-Whitney U test were used to assess the difference between the groups with and without diabetic complications. The range of values between the beginning and  end of the study was evaluated using Student’s t-test or Wilcoxon U test. The significance level was set at 5%.RESULTS: The initial sample consisted of 49 patients aged 59±9 years with a body mass index of 29.8±5.1 kg/m2, who have had diabetes for a median time of 36 months (interquartile range of 1-240) and have been on metformin for a median time of 36 months (interquartile range of 1-180). Twenty-five patients left the study between the second and fourth meetings. Malondialdehyde levels differed between before and after pharmacotherapeutic follow-up, being positively correlated with blood glucose, glycohemoglobin, and triglyceride level, and negatively correlated with metformin and superoxide dismutase. Blood glucose, glycohemoglobin, and malondialdehyde levels increased, whereas metformin levels decreased in the group with diabetic complications, and there was a correlation between malondialdehyde and the number of diabetic complications per patient.CONCLUSIONS: In this sample of patients with type 2 diabetes mellitus treated with metformin, oxidative stress was more pronounced in those with poor glycemic control and diabetic complications.

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