Beneficial Effect of the SGLT2 Inhibitor Empagliflozin on Glucose Homeostasis and Cardiovascular Parameters in the Cohen Rosenthal Diabetic Hypertensive (CRDH) Rat

2018 ◽  
Vol 23 (4) ◽  
pp. 358-371 ◽  
Author(s):  
Firas Younis ◽  
Jonathan Leor ◽  
Zaid Abassi ◽  
Natalie Landa ◽  
Lea Rath ◽  
...  

The effectiveness of empagliflozin (EMPA), a sodium glucose cotransporter type 2 inhibitor, on the kidney, pancreas, and heart was investigated in the Cohen Rosenthal diabetic hypertensive rat model (CRDH rat). Six-week-old CRDH male rats were fed a sugar diet (SD) and treated with the compound EMPA (group Drug/SD) or respective comparator with vehicle (group Veh/SD). A control group was fed a regular diet without treatment (group Veh/P). Preventive treatment with EMPA was measured during 4 months of follow-up. The treatment effect was evaluated according to results observed after 4 months in group Drug/SD when compared to those in group Veh/SD. Significant effect resulted in the following parameters: enhancement of urinary glucose excretion in association with diuresis; amelioration of postprandial hyperglycemia and fasting blood glucose levels; and decrease in calculated Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) as well as lower systolic and diastolic blood pressures. At the end of treatment, EMPA preserved nephrin integrity in the kidney, reduced proteinuria, and prevented diabetes-induced damage to glomerular diaphragm structure. In the pancreas, EMPA demonstrated an impressive decrease in fatty infiltration and atrophy. Blood pressure was significantly reduced in the EMPA-treated group (15 ± 5.1 mm Hg, P < .05) in contrast to the vehicle and control groups. Finally, compared to controls, EMPA significantly reduced left ventricle (LV) mass and LV systolic dilatation, according to 2-dimensional echocardiography. The importance of the study lies in demonstrating the efficacy of an antidiabetic drug with beneficial effects on blood pressure, weight, kidney, and pancreas and a positive effect on the heart.

Author(s):  
Babatunde Adebola Alabi ◽  
Temidayo Olutayo Omobowale ◽  
Ademola Oyagbemi ◽  
Ileri-Oluwa Busayo Emmanuel ◽  
Adeolu Adedapo ◽  
...  

Background and Aim: Corchorus olitorius (CO) leaf was reported to possess abundant antioxidants and used in the traditional treatment of heart disease. Previous studies revealed the protective roles of antioxidants against oxidative stress and inflammation, which are important underlying pathogenesis of myocardial injury that leads to infarction and heart failure. Therefore, CO leaf was chosen to evaluate its cardio-protective effects against ischemic-induced myocardial injury. Materials and Methods: Thirty male rats (Wistar strains) were divided into five groups (n = 6): normal control group, myocardial injury control group, pretreatment groups (250 and 500 mg/kg), positive control group (10 mg/kg enalapril). After pre-treatment of rats with ethanol leaf extract of CO for 19 days, Isoprenaline (100 mg/kg) administration induced acute myocardial injury and parameters like blood pressure, electrocardiogram, lipid peroxidation, antioxidants were assessed and tissue subjected to histological evaluations. Results: Isoproterenol given through subcutaneous significantly (p<0.05) reduced blood pressure and electrocardiography showed reduced p-interval and prolongation of QRS-interval in rats.               The extract significantly increased the blood pressure and p-interval, QRS-interval were significantly reduced. The significant increase in tissue malondialdehyde, serum         myeloperoxidase, creatine kinase-MB, lactate dehydrogenase and expression of Bax in the infarction control rats was decreased (p<0.05) in pre-treatment rats. Pre-treatment also increased glutathione-s-transferase, reduced glutathione and non-protein thiol level significantly. In contrast to cardio-injury control, histology showed mild level of inflammation and fatty infiltration in pre-treated rats. Conclusion: This study showed the protective role of ethanol extract of CO against myocardial injury through anti-apoptotic, antioxidant, anti-inflammatory and anti-arrhythmic effect. 


2017 ◽  
Vol 2 (4) ◽  
pp. 172-177
Author(s):  
Saeid Tanoorsaz ◽  
Naser Behpoor ◽  
Vahid Tadibi

Introduction: Cardiac apoptosis is one of the most important cardiovascular complications of diabetes. We aimed to investigate the changes of caspase-8, Bcl-2, and N-terminal pro B-type natriuretic peptide (NT-proBNP) in cardiac tissue after 4 weeks of aerobic exercise in male rats with diabetes. Methods: Forty adult male rats were randomly allocated to healthy control, diabetes, control + exercise and exercise + diabetes groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) solution (55 mg/kg). Two weeks after injection, fasting blood glucose levels were measured. After the induction of diabetes, the exercise program was performed for 4 weeks (5 sessions per week) at a speed of 15 to 18 m/min for 25 to 44 minutes. Forty-eight hours after the last training session, the subjects were anesthetized and the heart muscle was removed. Caspase-8, Bcl-2 and NT-proBNP levels were measured by ELISA method. Results: The induction of diabetes in the control group resulted in a significant increase in caspase-8, and NT-proBNP levels while an insignificant increase was observed for Bcl-2 levels (P<0.05). In non-diabetic groups, exercise caused no changes in caspase-8, NT-proBNP and Bcl-2 (P<0.05). Exercise in diabetic groups significantly decreased NT-proBNP while no changes were observed in caspase-8 and Bcl-2 (P<0.05). Conclusion: Our findings showed that diabetes increases the pro-apoptotic and anti-apoptotic agent. In addition, 4 weeks of regular aerobic exercises can be used as a non-pharmacological strategy to reduce the complications of apoptosis in diabetic cardiomyocytes.


2019 ◽  
Vol 32 (12) ◽  
pp. 1178-1185 ◽  
Author(s):  
Yukako Tatsumi ◽  
Akiko Morimoto ◽  
Kei Asayama ◽  
Nao Sonoda ◽  
Naomi Miyamatsu ◽  
...  

Abstract BACKGROUND Relationships between blood glucose (BG) levels and insulin action, and incidence of hypertension have not been well known epidemiologically. This study aimed to investigate the association between indices of diabetes and the incidence of hypertension and compare the predictive powers of these indices in middle-aged Japanese. METHODS This 5-year cohort study included 2,210 Japanese aged 30–64 years without hypertension. Hazard ratios of high fasting blood glucose (FBG) levels, high post-loaded BG levels, high glycated hemoglobin (HbA1c) levels, insulin resistance (defined by homeostasis model assessment of insulin resistance [HOMA-IR]) and impaired insulin secretion at baseline for the incidence of hypertension were estimated using multivariable-adjusted Cox proportional hazard models. Hypertension was defined as blood pressure ≥ 140/90 mm Hg or receiving antihypertensive treatment. RESULTS During the follow-up, 456 participants developed hypertension. After adjustment for HbA1c and HOMA-IR, FBG was independently and significantly associated with hypertension. The hazard ratio of participants with FBG ≥ 7.0 mmol/l was 1.79 compared with those with FBG < 5.6 mmol/l. Even among those with HbA1c < 6.5%, HOMA-IR < 2.5, body mass index < 25 kg/m2, age < 55 years old, blood pressure < 130/80 mm Hg or non- and moderate drinking, the results were similar. High 120-minute BG level and impaired insulin secretion did not increase the risk for hypertension. CONCLUSIONS FBG was a predictable index for future incidence of hypertension in middle-aged Japanese men and women. This is the first study comparing predictive powers of indices of diabetes for the incidence of hypertension.


2018 ◽  
Vol 36 (3) ◽  
pp. 162-169 ◽  
Author(s):  
Danchun Lan ◽  
Nenggui Xu ◽  
Jian Sun ◽  
Zhixing Li ◽  
Rongzhen Liao ◽  
...  

Objective To investigate the effect of electroacupuncture (EA) on endothelial dysfunction related to high fat diet (HFD)-induced insulin resistance through the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signalling pathway. Methods Twenty-four male Sprague-Dawley rats were fed a regular diet (Control group, n=8) or a HFD (n=16) for 12 weeks to induce an insulin resistance model. HFD-fed rats were divided into two groups that remained untreated (HFD group, n=8) or received electroacupuncture (HFD+EA group, n=8). EA was applied at PC6, ST36, SP6 and BL23. At the end of the experiment, fasting blood glucose (FBG), serum insulin (FINS), serum C-peptide (C-P) and homeostatic model assessment of insulin resistance (HOMA-IR) indices were determined. Pancreatic islet samples were subjected to histopathological examination. The thoracic aorta was immunostained with anti-rat insulin receptor substrate (IRS)-1, Akt and endothelial nitric oxide synthase (eNOS) antibodies. mRNA and protein expression of IRS-1, PI3K, Akt2 and eNOS in the vascular endothelium were determined by real-time PCR and Western blot analysis, respectively. Results The bodyweight increase of the HFD+EA group was smaller than that of the untreated HFD group. Compared with the HFD group, the levels of FBG, FINS, C-P and HOMA-IR in the HFD+EA group decreased significantly (P<0.01). Histopathological evaluation indicated that EA improved pancreatic islet inflammation. The expression of endothelial markers, such as IRS-1, PI3K, Akt2 and eNOS, decreased in the HFD group, while EA treatment appeared to ameliorate the negative impact of diet. Conclusion EA may improve insulin resistance and attenuate endothelial dysfunction, and therefore could play a potential role in the prevention or treatment of diabetic complications and cardiovascular disease through the PI3K/Akt signalling pathway.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 5-5
Author(s):  
Bahram Arjmandi ◽  
Kelli George ◽  
Lauren Ormsbee ◽  
Neda Akhavan ◽  
Joseph Munoz ◽  
...  

Abstract Objectives Osteoporosis is a public health concern for both women and men. Chronic inflammation contributes to bone loss; therefore, foods rich in antioxidants, such as prunes, are of great interest. Previously, dietary intervention with prunes has been shown to prevent orchidectomy-induced decreases in BMD, microstructure, and biomechanics in male rats; however, there is a need for this to be studied in a clinical setting in adult males. Methods Thirty-five men between the ages of 55 and 80 with moderate bone loss were included. The men were randomized into one of three groups: 100 g prunes daily, 50 g prunes daily, or control group. All three groups also consumed a multivitamin containing 450 mg calcium and 800 IU vitamin D. Serum samples from the baseline and three-month time points were analyzed for biomarkers of bone turnover, inflammation, and oxidative stress. Results After three months, daily consumption of 100 g prunes was associated with a significant decrease in serum concentrations of osteocalcin (P &lt; 0.001). Consumption of 50 g of prunes was associated with significant decreases in systolic blood pressure, and serum osteocalcin concentrations (P = 0.040), and an increase in the OPG: RANKL ratio (P = 0.041). There were also significant decreases in systolic blood pressure, OPG (P = 0.004), RANKL (P = 0.010), and osteocalcin (P = 0.049) in control group. There was a significant group*time effect for changes in OPG (P = 0.019) and the OPG: RANKL ratio (P = 0.029). Conclusions Decreases in osteocalcin indicate a decrease in bone turnover, and a higher OPG: RANKL ratio indicates that more RANKL is bound to OPG, and not to osteoclasts, thus downregulating osteoclast activity. Therefore, regular consumption of either 100 g or 50 g dried plum for three months may make some contributions to bone formation and bone turnover activity, and minimal contribution to decreasing inflammation and improving bone density and quality. Funding Sources USDA/NIFA, California Prune Board, and Shaklee.


2005 ◽  
Vol 33 (03) ◽  
pp. 449-457 ◽  
Author(s):  
Hirozo Goto ◽  
Yohei Sasaki ◽  
Hirotoshi Fushimi ◽  
Naotoshi Shibahara ◽  
Yutaka Shimada ◽  
...  

Curcuma herbs have a vasodilator effect. The effects of C. longa, which induces only endothelium-independent vasodilatation, and C. zedoaria, which induces both endothelium-dependent and -independent vasodilatation, were studied on vasomotion and hemorheology in spontaneously hypertensive rats. Spontaneously hypertensive eight-week-old male rats were assigned to five groups. For 12 weeks, the control group received standard chow. The 3%CL (C. longa) group received standard chow containing 3% (wt/wt) C. longa. The 1%CZ and 3%CZ (C. zedoaria) groups received standard chow containing 1% and 3% (wt/wt) C. zedoaria, respectively. The captoril group received standard chow and 100 mg/kg/day of captoril in drinking water. Blood pressure, vasomotion, hemorheology, etc. were examined. Systolic blood pressure of the 3%CZ and captoril groups decreased significantly as compared to the control group. Acetylcholine-induced endothelium-dependent relaxations of the 3%CZ and captoril groups were increased to a greater degree, significantly, than the control group. When testing xanthine oxidase-induced contraction, the 3%CZ group was significantly decreased as compared to the control group. Low shear stress of whole blood viscosity showed the 3%CL and 3%CZ groups to be decreased significantly compared to the control group. Thus, Curcuma herbs have hypotensive and protective effect on the endothelium in spontaneously hypertensive rats. Especially, C. zedoaria is more effective than C.longa, and its mechanism is thought to be related to a radical scavenging effect and improvement of hemorheology.


2020 ◽  
Author(s):  
Shakiba Naiemian ◽  
Mohsen naeemipour ◽  
Mehdi Zarei ◽  
Ali Gohari ◽  
Mohammad Reza Behroozikhah ◽  
...  

Abstract Background: Asprosin, a newly identified adipokine, is pathologically increased in individuals with insulin resistance. However, the available evidence on the association of asprosin and type 2 diabetes mellitus (T2DM) status is still scarce. Therefore, this study aimed to determine the relationship between serum concentrations of asprosin and T2DM status . Methods: This observational study was performed based on 194 adults (97 newly diagnosed T2DM and 97 healthy individuals). Anthropometric and biochemical variables were determined in all participants . Serum concentrations of asprosin were measured using enzyme-linked immunosorbent assay (ELISA). Results: In patients with T2DM, the serum concentrations of asprosin were significantly higher than the healthy controls (4.18 [IQR: 4.4] vs. 3.5 [IQR: 1.85], P< 0.001). The concentrations of asprosin were significantly correlated with body mass index (BMI) and fasting blood glucose (FBG) in healthy subjects and with BMI, FBG, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin check index (QUICKI), triacylglycerol (TAG) and total cholesterol/ high-density lipoprotein cholesterol (TC/HDL-C) ratio in the T2DM group. In fully adjusted model, the odds ratio (OR) of T2DM with serum concentrations of asprosin was approximately 1.547 (95% CI 1.293-1.850, P< 0.001) compared to the control group . Multiple stepwise regression analysis indicated that FBG and HOMA-IR were independently associated with asprosin in T2DM. Conclusion : Our findings indicated that serum concentrations of asprosin are increased in patients with T2DM. Also, asprosin is correlated with insulin resistance and TC/HDL-C ratio (atherosclerotic risk factor of cardiovascular diseases) in patients with T2DM.


2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Derun Gao

Objective In recent years, a large number of experimental studies have shown that the proliferation and migration of VSMC are the pathological basis of various vascular diseases, including AS, hypertension, and restenosis after angioplasty. It’s rather remarkable that Phenotypic Modulation of VSMC plays an important role in their proliferation and migration. Myocardin is a key transcription factor for the differentiation of VSMC by far, which can effectively activate the differentiation process of SMC. Many studies have shown that endurance training is an effective way to improve glucose and lipid metabolism. This study attempted to explore the effects of long-term external stress (endurance training) on arterial smooth muscle phenotype modulation and myocardin through secondary vascular disease, in order to provide theoretical support and practical basis for sports therapy in T2DM secondary diseases. Methods Male SD rats were randomly divided into the general feed group (pC) and the high-sugar and high-fat feed group (pD). After 7 weeks, rats in pD were injected a small doses of streptozotocin through abdominal cavity. Those Non-fasting Blood Glucose (NFBG) ≥16.7mmol/L after 72h and with insulin resistance were diagnosed as diabetes. Thereafter, the pC group was randomly divided into a blank control group (C), an endurance training group (E), a diabetes model group (D), and a diabetic+endurance training group (DE). No load platform training was conducted in E&DE group, 5 days per week for 8 weeks. 8 weeks after, BP was measured through left common carotid artery intubation, blood sugar was test by enzyme chemical assay, α-SM-actin, SM-MHC , SM22α,Myocardin and KLF4 were measured through ELISA.  Results 1. Compared with C, MCP (carotid blood pressure) of D increased significantly, FBG and FINS decreased significantly, expression of α-SM-actin, SM-MHC, SM22α and Myocardin Significantly dropped, KLF4 rose significantly. Compared with D, the expression of FBG in E was significantly down-regulated, FINS was significantly up-regulated, and the expression of α-SM-actin, SM22α and Myocardin was significantly up-regulated. Conclusions 8 weeks of endurance training significantly increased the expression level of contractile protein in the aorta smooth muscle of diabetic rats, making the smooth muscle phenotype changed from synthetic to contractile type, which effectively inhibited the excessive proliferation and migration of smooth muscle cells.Myocardin is one of the hot spots in the study of vascular differentiation in recent years. This study shows that the role of endurance training in improving plaque formation and lowering blood pressure may be produced by regulating myocardin.


2012 ◽  
Vol 1 (2) ◽  
pp. 68-73
Author(s):  
R Eldeeb ◽  
MH Gamal-Eldin ◽  
EA Khowailed ◽  
MM Fathy ◽  
N Shantakumari ◽  
...  

Background: The excess usage of fructose as a sweetener has raised the incidence of insulin resistance among the population which is associated with dyslipedemia, hypertension and obesity. This work studied the effect of induced insulin resistance on body weight, blood pressure, lipid profile, glycemic state and lipolytic activity of adipose tissue in male rats. Methods: Twenty male rats of 129.4 g average body weight (BW) were divided equally into two groups. Both had free access to water. The control group had pure water; the experimental group had water mixed with 25% of fructose to induce insulin resistance. After 3 months body weight, blood pressure, fasting blood glucose, insulin levels, lipid profile of both groups were measured and lipolytic activity of adipose tissue was assessed. Results: Rats given fructose for 3 months showed significant increase in BW, systolic blood pressure, triglyceride, Cholesterol, low density lipoprotein, fasting blood glucose and insulin levels with a significant decline in highdensity lipoprotein. Lipolytic activity of subcutaneous (SC) and visceral adipose tissue in presence of adrenaline increased significantly which runs in parallel with the results obtained in presence of insulin as it showed a significant rise in both SC and visceral adipose tissue. Data were considered statistically significant at alpha level of 5%. Conclusion: Insulin resistance induced in male rat by high fructose consumption showed a significant rise in BW and is associated with hypertension and dyslipidemia with significant rise in lipolytic activity of both SC and visceral adipose tissue. DOI: http://dx.doi.org/10.3126/njms.v1i2.6602 Nepal Journal of Medical Sciences. 2012;1(2): 68-73


2018 ◽  
Vol 72 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Valeria Calcaterra ◽  
Hellas Cena ◽  
Pietro Mariano Casali ◽  
Gianluca Iacobellis ◽  
Riccardo Albertini ◽  
...  

Background: Cardiovascular risk is reported in disabled children and epicardial fat (EF) is considered an independent predictor of cardiovascular disease (CVD). No data on the EF thickness (EFT) evaluation in disabled children have been published. Objective: We investigated EFT in neurologically impaired (NI) children; its relationship with their metabolic profile was also considered. Methods: Clinical data, body composition estimation, biochemical profile, and ultrasound-measured EFT were performed in 32 disabled patients (12.4 ± 6.3 years). Pathological parameters were defined using the following criteria: waist circumference >95th percentile, waist to height ratio (WHtR) >0.5, total cholesterol and triglycerides (TG) values >95th percentile, high density lipoprotein cholesterol <5th percentile, fasting blood glucose >100 mg/dL, homeostasis model assessment for insulin resistance (HOMA) >97.5th percentile, and EFT >3.6 mm. Results: EFT values in NI children were higher compared with control group values (p = 0.02). EFT correlated with gender (p < 0.001), age (p = 0.02), pubertal stage (p = 0.04), as well as WHtR (p = 0.03). A correlation between EFT and leptin was also noted (p = 0.04). EFT levels significantly correlated with pathological TG (p = 0.01) and HOMA-IR (p = 0.04). Conclusions: Higher EFT was observed in NI children compared with controls. EFT values correlated with clinical, metabolic, and endocrinological parameters. Ultrasound-measured EFT could be used to promptly detect subclinical CVD and to prevent adverse outcomes in disabled children.


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