scholarly journals P0964EFFECTS OF XANTHINE OXIDASE INHIBITORS AND DAPAGLIFLOZIN ON RENAL GLUCOSE AND URATE TRANSPORTERS IN METABOLIC SYNDROME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hwee-Yeong Ng ◽  
Chien-Te Lee ◽  
Foong-Fah Leung ◽  
Yuai-Ting Lee
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Uric Acid ◽  
Xanthine Oxidase ◽  
Resistance Index ◽  
High Fructose Diet ◽  
Insulin Resistance Index ◽  
Xanthine Oxidase Inhibitors ◽  
High Fructose ◽  
Uric Acid Transporters

Abstract Background and Aims Metabolic syndrome consists of several medical conditions that collectively predict the risk for cardiovascular disease. Hyperglycemia and hyperuricemia are the major disorders of metabolic syndrome. Kidney reabsorbs almost all filtrated glucose by active transport at normal concentrations of plasma glucose via members of the sodium glucose transport (SGLT) family. Besides, the kidney plays a pivotal role in handling uric acid homeostasis. Uric acid is mainly controlled by urate transporter (UAT), urate anion exchanger 1 (URAT1) and glucose transporter 9 (GLUT9). The aims of the study were to determine the alteration of renal glucose and uric acid transporters in animals with metabolic syndrome after treatment of xanthine oxidase inhibitors and SGLT2 inhibitor. Method Sprague-Dawley rats were fed with normal chow (Control) or high fructose diet (60%) for totally 6 months. For those animals fed with high fructose diet for 3 months, they were divided into 4 groups including high fructose diet without treatment (FR), treatment with allopurinol (150 mg/L in drinking water), with febuxostat (30 mg/L in drinking water) or with dapagliflozin (1mg/kg/day intraperitoneal injection). Blood, urine and blood pressure were collected and measured at the end of study. Gene and protein expression of renal glucose and uric acid transporters were determined by reverse transcriptase polymerase chain reaction. The changes of transporters were then confirmed by immunohistochemical staining. Results High-fructose diet induced higher levels of fasting glucose, insulin resistance index, uric acid, triglyceride and blood pressure in FR group (all p <0.05 vs. control). Treatment of allopurinol, febuxostat and dapagliflozin reduced body weight significantly. Fasting glucose, insulin resistance index and hyperuricemia were improved in all drug treatment groups (all p <0.05). In the kidney, high fructose diet significantly upregulated SGLT1, SGLT2 and GLUT2 but downregulated GLUT1 expression. Urate transporters, including GLUT9, UAT and URAT1 were also increased (p <0.05). The improvement of insulin resistance by xanthine oxidase inhibitors was associated with suppression of renal SGLT1, SGLT2 and GLUT2 expression. Dapagliflozin alleviated hyperuricemia and induced uricosuria without affecting serum xanthine oxidase activity. Compared to FR, dapagliflozin significantly inhibited fructose-induced overexpression of GLUT9, UAT and URAT1 in the kidney. Conclusion Long term high fructose diet induced metabolic syndrome in rats. Treatment of xanthine oxidase inhibitors and dapagliflozin ameliorated components of metabolic syndrome. Both allopurinol and febuxostat improved insulin resistance in association with suppression of renal SGLT1, SGLT2 and GLUT2 expression. Although dapagliflozin and xanthine oxidase inhibitors reduced uric acid in different mechanisms, they shared a similar molecular changes in the kidney by downregulating GLUT9, UAT and URAT1 expression.

scholarly journals Prevention of insulin resistance with Hibiscus sabdariffa Linn. extract in high-fructose fed rat

2015 ◽  
Vol 23 (4) ◽  
pp. 192-6
Author(s):  
Trinovita Andraini ◽  
Sophie Yolanda
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Resistance Index ◽  
Insulin Level ◽  
Hibiscus Sabdariffa ◽  
Blood Insulin ◽  
High Fructose Diet ◽  
Insulin Resistance Index ◽  
High Fructose

Background: Dyslipidemia and stress oxidative play an important role as the cause of insulin resistance. One herb that has potent antioxidant effect and may improve dyslipidemia is Hibiscus sabdariffa Linn. The aim of this study was to evaluate the effect of Hibiscus sabdariffa Linn. extract on fasting blood glucose level, fasting blood insulin level, and insulin resistance index (HOMA-IR) in high-fructose fed rat.Methods: This was an experimental study in 25 Sprague-Dawley rats which were administered with a high-fructose diet (10% ad libitum) and Hibiscus sabdariffa Linn. extract at a dose of 100, 200, and 400 mg/kgBW/d simultaneously for 5 weeks. At the end of study, fasting blood glucose level, fasting blood insulin level and insulin resistance index (HOMA-IR) were measured.Results: Fasting blood glucose, blood insulin, and HOMA-IR level of rats given high-fructose diet with Hibiscus sabdariffa Linn. at dose 100 mg/kgBW/d were not significantly different than the group of rats given only high-fructose fed. While at the dose of 400 mg/kgBW/d, they were significantly lower than the group given only high-fructose fed (4.84 mmol/L vs 6.11 mmol/L, 0.07 µU/L vs 0.3 µU/L, and 0.02 vs 0.08 respectively).Conclusion: Oral administration of Hibiscus sabdariffa Linn. could prevent the development of insulin resistance induced by high-fructose diet in the rat.

scholarly journals Serum uric acid and its association with metabolic syndrome and carotid atherosclerosis in obese children

2009 ◽  
Vol 160 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Lucia Pacifico ◽  
Vito Cantisani ◽  
Caterina Anania ◽  
Elisabetta Bonaiuto ◽  
Francesco Martino ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Uric Acid ◽  
Carotid Atherosclerosis ◽  
Resistance Index ◽  
Model Assessment ◽  
Obese Children ◽  
Pubertal Stage ◽  
Carotid Imt

ObjectiveThe association between hyperuricemia, metabolic syndrome (MS), and atherosclerotic vascular disease has been reported in adults, but very little is known about this association in children. The aims of our study were to ascertain the correlates of uric acid (UA) in a sample of obese children, and to investigate whether UA is associated with carotid intima-media thickness (IMT) independently from classical risk factors including MS.MethodsWe analyzed carotid IMT along with serum triglycerides, total and high-density lipoprotein cholesterol, glucose, insulin, insulin resistance index (as homeostasis model assessment of insulin resistance), alanine aminotransferase, γ-glutamyltransferase, creatinine, and UA in 120 obese children and 50 healthy control children.ResultsUA concentrations were significantly higher in obese children compared with controls; moreover, they correlated with the most established cardiovascular risk factors. In the group of obese children, after adjustment for age, sex, pubertal stage, and creatinine, an independent association between UA levels and the presence of MS syndrome was observed (unstandardized coefficient, 0.044 (95% confidence intervals (CI) 0.015–0.072); P<0.01). Carotid IMT significantly increased in the fourth quartile of UA compared with that in the first, second, and third quartile (0.49 (0.46–0.53), 0.53 (0.49–0.56), and 0.55 (0.52–0.59) vs 0.61 (95% CI, 0.58–0.64); P<0.01). When multivariate analysis was performed after adjusting for age, gender, pubertal stage, creatinine, and MS (considered as a single clinical entity), or the individual components of MS simultaneously included, the association between UA and carotid IMT was significant (P<0.01).ConclusionsIn obese children and adolescents, increased UA levels are associated with carotid atherosclerosis.

CHRONIC AEROBIC EXERCISE PREVENTS HIGH-FRUCTOSE DIET-INDUCED IMPAIRMENT IN BLOOD PRESSURE IN HEALTHY YOUNG ADULTS: A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

2021 ◽  
pp. 1-41
Author(s):  
Alexandra Ferreira Vieira ◽  
Cesar Eduardo Jacintho Moritz ◽  
Thiago Rozales Ramis ◽  
Francesco Pinto Boeno ◽  
Gabriela Cristina dos Santos ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Young Adults ◽  
Body Weight ◽  
Uric Acid ◽  
Aerobic Exercise ◽  
Pancreatic Beta Cell ◽  
Resistance Index ◽  
Sensitivity Index ◽  
High Fructose Diet ◽  
High Fructose

Abstract The purpose of the study was to verify the effect of 4 weeks of a high-fructose diet associated with aerobic training on the risk factors for cardiometabolic diseases. Twenty-one young adults were randomized into three groups: high-fructose diet (HFD: 1 g/kg body weight of fructose/day), high-glucose diet (HGD: 1 g/kg body weight of glucose/day), and high-fructose diet and exercise (HFDE: 1 g/kg body weight of fructose/day + 3 weekly 60-minute sessions of aerobic exercise). Before and after the 4 weeks of the intervention, blood samples were taken and flow-mediated dilatation, insulin resistance index, pancreatic beta cell functional capacity index, insulin sensitivity index, and 24-hour blood pressure were evaluated. HFD showed an increase in uric acid concentrations (p = 0.040), and HGD and HFDE groups showed no changes in this outcome between pre- and post-intervention; however, the HFDE group showed increased uric acid concentrations from the middle to the end of the intervention (p = 0.013). In addition, the HFD group showed increases in nocturnal systolic blood pressure (SBP) (p = 0.022) and nocturnal diastolic blood pressure (DBP) (p = 0.009). The HGD group exhibited decreases in nocturnal SBP (p = 0.028) and nocturnal DBP (p = 0.031), and the HFDE group showed a decrease in 24-hour SBP (p = 0.018). The consumption of 1 g/kg of fructose per day can increase uric acid concentrations and blood pressure in adults. Additionally, aerobic exercises along with fructose consumption attenuate changes in uric acid concentrations and prevent impairment in nocturnal blood pressure.

Are Insulin Resistance Index, IGF-1 and Metabolic Syndrome Components Correlates with Severe Preeclampsia?

2010 ◽  
Vol 30 (3) ◽  
pp. 302-310 ◽  
Author(s):  
Edimárlei Gonsales Valério ◽  
Ana Lúcia Letti Müller ◽  
Sérgio Hofmeister Martins-Costa ◽  
José Geraldo Lopes Ramos ◽  
Gustavo Rodini
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Resistance Index ◽  
Severe Preeclampsia ◽  
Insulin Resistance Index ◽  
Metabolic Syndrome Components

Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population

2002 ◽  
Vol 103 (2) ◽  
pp. 137-142 ◽  
Author(s):  
Yukihiro YAMAMOTO ◽  
Hiroshi HIROSE ◽  
Ikuo SAITO ◽  
Motowo TOMITA ◽  
Matsuo TANIYAMA ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Uric Acid ◽  
Adiponectin Level ◽  
Density Lipoprotein ◽  
Resistance Index ◽  
Hdl Cholesterol ◽  
Serum Adiponectin ◽  
Serum Adiponectin Level ◽  
Insulin Resistance Index

Adiponectin, which is secreted specifically by adipose tissue, has been shown to act as an anti-atherosclerotic protein by direct effects on endothelial cells. Clinical studies have shown that adiponectin levels are lower in individuals with obesity, diabetes and coronary artery disease. The present study investigated relationships between serum adiponectin levels and body mass index (BMI), blood pressure, insulin resistance index, lipid profile, uric acid and high-sensitivity C-reactive protein levels in a large number of Japanese subjects not taking any medication for metabolic disease and without severe illness (705 men and 262 women; age 30–65 years; BMI 22.5±2.9kg/m2). The serum adiponectin concentration was measured by ELISA, without a protein-denaturing step. The insulin resistance index was assessed by homoeostasis model assessment (HOMA-IR). The serum concentration of adiponectin in women (13.5±7.9μg/ml) was significantly higher than that in men (7.2±4.6μg/ml). The serum adiponectin level was negatively correlated with BMI, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, total cholesterol, triacylglycerols, low-density lipoprotein (LDL)-cholesterol and uric acid, and positively correlated with high-density lipoprotein (HDL)-cholesterol. The correlations between serum adiponectin level and insulin, HOMA-IR, triacylglycerols, HDL-cholesterol, LDL-cholesterol and uric acid were significant even after adjustment for age, sex and BMI. Stepwise multiple regression analysis revealed that HDL-cholesterol, sex, BMI and HOMA-IR were independently correlated with the serum adiponectin level (R2 = 0.377). These findings suggest that the serum adiponectin level is negatively correlated with HOMA-IR and positively correlated with HDL-cholesterol, independent of age, sex and BMI, in the Japanese population.

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