Abstract 17853: Activation of AMP-activated Protein Kinase (AMPKα) by AICAR Attenuates Klotho Deficiency-induced Endothelial Dysfunction, Arterial Stiffening and Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yi Lin ◽  
Zhongjie Sun

Background: Arterial stiffening and hypertension are progressive aging-related disorders. Klotho (KL) is a recently-discovered anti-aging gene but its role in the pathogenesis of endothelial dysfunction, arterial stiffening and hypertension is not fully understood. Methods and Results: Heterozygous Klotho deficiency ( KL +/- ) mice and WT littermate mice were fed on high fat diet (HFD) or normal diet (ND). Plasma KL in KL heterozygeous mice (+/-) is about a half of that of the WT mice. Pulse wave velocity (PWV), an index of arterial stiffening, was increased in KL +/- mice but not in WT mice fed on HFD for 4 weeks. Systolic blood pressure and blood glucose levels were increased earlier with greater magnitudes in KL +/- mice than in WT mice fed on HFD. Notably, protein expression of collagen I, Runx2, and TGFβ1 were increased but protein expression of phosphorylated AMPKα (pAMPKα), phosphorylated eNOS (peNOS), and Mn-SOD were decreased in aortas of KL +/- mice fed on HFD for 5 weeks. Interestingly, daily injection of AICAR, an activator of AMPK, abolished the increases in PWV, blood pressure, and blood glucose in KL +/- mice fed on HFD. AICAR not only abolished the downregulation of pAMPKα, peNOS, and Mn-SOD levels but also attenuated the increased levels of collagen I, Runx2, TGFβ1 and superoxide, elastic lamellae breaks, and calcification in aortas in KL +/- mice fed on HFD. Conclusions: Klohto deficiency promotes HFD-induced endothelial dysfunction, arterial stiffening and hypertension. The promoting effects of klotho deficiency on arterial stiffening may be due to downregulation of endothelial AMPKα activity.

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1191 ◽  
Author(s):  
Yumi Nakamura ◽  
Hiroshi Watanabe ◽  
Aiko Tanaka ◽  
Masato Yasui ◽  
Jun Nishihira ◽  
...  

Increased hydration is recommended as healthy habit with several merits. However, supportive data are sparse. To assess the efficacy of increased daily water intake, we tested the effect of water supplementation on biomarkers in blood, urine, and saliva. Twenty-four healthy Japanese men and 31 healthy Japanese women with fasting blood glucose levels ranging from 90–125 mg/dL were included. An open-label, two-arm, randomized controlled trial was conducted for 12 weeks. Two additional 550 mL bottles of water on top of habitual fluid intake were consumed in the intervention group. The subjects drank one bottle of water (550 mL) within 2 h of waking, and one bottle (550 mL) 2 h before bedtime. Subjects increased mean fluid intake from 1.3 L/day to 2.0 L/day, without changes in total energy intake. Total body water rate increased with associated water supplementation. There were no significant changes in fasting blood glucose and arginine vasopressin levels, but systolic blood pressure was significantly decreased in the intervention group. Furthermore, water supplementation increased body temperature, reduced blood urea nitrogen concentration, and suppressed estimated glomerular filtration rate reduction. Additionally, existence of an intestinal microbiome correlated with decreased systolic blood pressure and increased body temperature. Habitual water supplementation after waking up and before bedtime in healthy subjects with slightly elevated fasting blood glucose levels is not effective in lowering these levels. However, it represents a safe and promising intervention with the potential for lowering blood pressure, increasing body temperature, diluting blood waste materials, and protecting kidney function. Thus, increasing daily water intake could provide several health benefits.


2018 ◽  
Vol 315 (6) ◽  
pp. E1264-E1273
Author(s):  
Ursula H. Neumann ◽  
Michelle M. Kwon ◽  
Robert K. Baker ◽  
Timothy J. Kieffer

It was long thought that the only hormone capable of reversing the catabolic consequences of diabetes was insulin. However, various studies have demonstrated that the adipocyte-derived hormone leptin can robustly lower blood glucose levels in rodent models of insulin-deficient diabetes. In addition, it has been suggested that some of the metabolic manifestations of insulin-deficient diabetes are due to hypoleptinemia as opposed to hypoinsulinemia. Because insulin therapy increases leptin levels, we sought to investigate the contribution of leptin to the beneficial effects of insulin therapy. To do this, we tested insulin therapy in streptozotocin (STZ) diabetic mice that were either on an ob/ ob background or that were given a leptin antagonist to determine if blocking leptin action would blunt the glucose-lowering effects of insulin therapy. We found that STZ diabetic ob/ ob mice have a diminished blood glucose-lowering effect in response to insulin therapy compared with STZ diabetic controls and exhibited more severe weight loss post-STZ injection. In addition, STZ diabetic mice administered a leptin antagonist through daily injection or plasmid expression respond less robustly to insulin therapy as assessed by both fasting blood glucose levels and blood glucose levels during an oral glucose tolerance test. However, leptin antagonism did not prevent the insulin-induced reduction in β-hydroxybutyrate and triglyceride levels. Therefore, we conclude that elevated leptin levels can contribute to the glucose-lowering effect of insulin therapy in insulin-deficient diabetes.


2017 ◽  
Vol 65 (4) ◽  
pp. 772-783 ◽  
Author(s):  
Jie Zhang ◽  
Lixin Guo

Postprandial hypotension (PPH) is a common condition that occurs primarily in elderly patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness of acarbose for PPH; it also investigated possible mechanisms behind PPH development. This single-blind, randomized controlled trial included 91 elderly patients with T2DM, aged between 60 and 80 years, who were inpatients at Beijing Hospital between March 2012 and November 2014. The patients were included into one of three groups: Group A, patients with T2DM without PPH; Group B, patients with T2DM with PPH receiving placebo; and Group C, patients with T2DM with PPH receiving acarbose. After an overnight fast, patients received a single dose of acarbose (100 mg) or placebo and then consumed a standardized 450 kcal meal. Blood pressure, glucose levels, heart rate (HR), and catecholamine levels were evaluated. Acarbose ameliorated PPH as determined by significant improvements in the duration and maximal fall in blood pressure (both p<0.001); however, no differences in HR and blood glucose levels were observed. In patients with PPH, blood pressure was correlated with blood glucose and HR variability values (p<0.05). Correlations between epinephrine and glucagon-like peptide-1 with blood pressure in groups A and C were largely lost in group B. Acarbose reduced postprandial blood pressure fluctuations in elderly patients with diabetes. PPH may be related to impaired autonomic nervous system function, reduced catecholamine secretion, and postprandial fluctuations in blood glucose levels.Trial registration numberChinese Clinical Trial Registry ChiCTR-IPR-15006177.


2021 ◽  
Vol 3 (2) ◽  
pp. 08-13
Author(s):  
Ervina Julien Sitanggang

Introduction: Cardiovascular disease is the number one cause of death globally with an incidence of adolescents and young adults in Indonesia as many as 153.705 cases. Central obesity is associated with the risk of cardiovascular disease due to increase in fasting blood glucose levels, cholesterol and triglyceride levels, and blood pressure. Aims: to determine the correlation between waist circumference and fasting blood glucose levels, triglyceride levels, and blood pressure in young adults. Method: This analytic study with a cross-sectional approach involved 53 young adult subjects (18-25 years old). Waist circumference is measured using a tape measure. Blood sugar and triglyceride levels were measured using Cobas® 6000 analyzer machine from blood samples of subjects after fasting for 8-12 hours. Blood pressure data are obtained by measurement using aneroid sphygmomanometer. Results: In this study, the mean waist circumference of the research subjects was 77,4 cm. No correlation was found between waist circumference and fasting blood sugar levels (p = 0,159). However, a positive correlation was found between waist circumference and triglyceride levels (p = 0,008; r = 0,332), between waist circumference and systolic blood pressure (p = 0,049; r = 0,230), and between waist circumference and diastolic blood pressure (p = 0,017; r = 0,293). Conclusion: waist circumference is positively correlated with triglyceride levels and blood pressure, but does not correlate with fasting blood sugar levels.


2020 ◽  
Vol 48 (4) ◽  
pp. 030006052091841
Author(s):  
Qianling Zhuang ◽  
Lirong Wu ◽  
Wang Ting ◽  
Lin Jie ◽  
Jingying Zou ◽  
...  

Objective The purpose of this study was to investigate negative emotions and factors related to the risk of mental disorders in individuals with prediabetes and hypertension. Methods A total of 504 community-dwelling adult men and women in Suzhou, China, were enrolled and questionnaires used to obtain sociodemographic data, anxiety and depression scores, and current status of common metabolic indicators, including blood glucose level and blood pressure. Results Anxiety and depression scores in participants with prediabetes and hypertension were significantly higher than those in participants with normal blood glucose levels and normal blood pressure. Correlation analysis revealed that age, sex, smoking, duration of disease, physical activity, blood pressure and fasting plasma glucose levels were key factors accelerating the progression to both anxiety and depression in all participants. Conclusions More attention should be paid to negative emotions in individuals with prediabetes and hypertension. These findings could help to inform health providers in developing interventions for this population.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Jussara M do Carmo ◽  
John N Freeman ◽  
Alexandre A da Silva ◽  
Zhen Wang ◽  
John E Hall

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of leptin signaling. Hypothalamic SOCS3 is upregulated in obese animals fed a high-fat diet and has been suggested to contribute to development of resistance to leptin’s anorexic effects. In this study we determined whether deletion of SOCS3 in the entire central nervous system (CNS) amplifies the chronic anorexic and blood pressure (BP) effects of physiological increases in plasma leptin in mice fed a normal diet. SOCS3 flox/flox -Nestin-cre mice were generated by breeding SOCS3 flox/flox with Nestin-cre mice. BP and heart rate (HR) were recorded by telemetry, and oxygen consumption (VO 2 ) was monitored by indirect calorimetry in 22-week-old SOCS3 flox/flox -Nestin-cre (n=4) and control mice (SOCS3 flox/flox , n=4). Compared to controls SOCS3 flox/flox -Nestin-cre mice were lighter (30±1 vs 33±1 g) and normoglycemic (124±7 vs 146±10 mg/dl), consumed less food (3.0±0.4 vs 3.6±0.2 g/day) and had similar VO 2 (77±6 vs 73±3 ml/kg/min). SOCS3 flox/flox -Nestin-cre mice had similar MAP (103±3 vs 107±3 mmHg) but higher HR (666±15 vs 602±17 bpm) compared to control mice. Chronic leptin infusion greatly reduced food in SOCS3 flox/flox -Nestin-cre (46±3 vs 35±4%) and increased MAP (15±3 vs 7±2 mmHg) and VO2 (18±3 vs 14±2%) compared to control mice. No significant changes were observed in HR in either group. Leptin infusion significantly reduced blood glucose levels in both groups (124±7 to 97±7 vs 146±10 to 105±7 mg/dl). These results indicate that SOCS3 deletion in the entire CNS reduces body weight and food intake, and amplifies leptin’s effect on appetite and blood pressure and also suggest the SOCS3 signaling attenuates the chronic actions of leptin on blood pressure as well as appetite regulation even in non-obese mice fed a normal diet. (NHLBI-PO1HL51971, NIGMS P20GM104357 and AHA SDG5680016)


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