Abstract 180: Downregulation of GRK2 by Long-Term Exercise Improves Vascular Insulin Sensitivity and Delays the Development of Hypertension in SHRs

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Haifeng Zhang ◽  
Wenjuan Xing ◽  
Feng Gao
Keyword(s):  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Physical Exercise ◽  
Critical Role ◽  
Training Session ◽  
Mesenteric Arteries ◽  
Whole Body ◽  
Wistar Kyoto

Aims: Exercise training, a recommended nonpharmacological strategy for hypertensive patients, exerts beneficial effect on blood pressure modulation, but the underlying mechanisms remain elusive. Vascular insulin resistance is an early pathologic alteration in hypertensive vascular injury and plays a critical role in the development of hypertension. This study aimed to investigate whether long-term physical exercise starting at prehypertensive period prevents the development of hypertension via improving vascular insulin sensitivity. Methods: Young (4-week-old) prehypertensive spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto controls (WKY) were subjected to a 10-week free-of-loading swim training session (60 min/day, 5 days/week). Insulin-induced mesenteric arteriolar vasorelaxation were determined. Results: SHRs showed higher systolic blood pressure (SBP) and decreased insulin sensitivity of the whole body and resistance vessels compared with those of WKY rats. SBP in the exercised SHRs was significantly lower than that in sedentary ones (180.2±5.1 vs. 205.7±3.7 mmHg, n=6, P<0.05). Vascular insulin sensitivity in mesenteric arteries was improved after exercise training as evidenced by increased vasodilation response to insulin (29.0%±2.5% vs. 18.4%±5.9% to 1 μmol/L insulin, n=6, P<0.05). In addition, exercise downregulated vascular GRK2 expression and activity, which further increased insulin-stimulated vascular Akt/eNOS activation in exercised SHRs. More importantly, suppression of GRK2 with siRNA mimicked the effect of exercise-enhanced vascular insulin sensitivity, while upregulation of GRK2 by Chariot-mediated delivery reversed the exercise-induced vascular insulin sensitization. Conclusions: Long-term regular physical exercise beginning at prehypertensive stage improves vascular insulin sensitivity via downregulating GRK2 and consequently delays the development of hypertension.

scholarly journals Long-term exercise attenuates blood pressure responsiveness and modulates kidney angiotensin II signalling and urinary sodium excretion in SHR

2011 ◽  
Vol 12 (4) ◽  
pp. 394-403 ◽  
Author(s):  
Silmara Ciampone ◽  
Rafael Borges ◽  
Ize P de Lima ◽  
Flávia F Mesquita ◽  
Elizabeth C Cambiucci ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Exercise Training ◽  
Sodium Excretion ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
Receptor Expression ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

Observations have been made regarding the effects of long-term exercise training on blood pressure, renal sodium handling and renal renin–angiotensin–aldosterone (RAS) intracellular pathways in conscious, trained Okamoto–Aoki spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKy) normotensive rats, compared with appropriate age-matched sedentary SHR and WKy. To evaluate the influence of exercise training on renal function and RAS, receptors and intracellular angiotensin II (AngII) pathway compounds were used respectively, and lithium clearance and western blot methods were utilised. The current study demonstrated that increased blood pressure in SHR was blunted and significantly reduced by long-term swim training between the ages of 6 and 16 weeks. Additionally, the investigators observed an increased fractional urinary sodium excretion in trained SHR (SHRT) rats, compared with sedentary SHR (SHRS), despite a significantly decreased creatinine clearance (CCr). Furthermore, immunoblotting analysis demonstrated a decreased expression of AT1R in the entire kidney of TSHR rats, compared with SSHR. Conversely, the expression of the AT2R, in both sedentary and trained SHR, was unchanged. The present study may indicate that, in the kidney, long-term exercise exerts a modulating effect on AngII receptor expression. In fact, the present study indicates an association of increasing natriuresis, reciprocal changes in renal AngII receptors and intracellular pathway proteins with the fall in blood pressure levels observed in TSHR rats compared with age-matched SSHR rats.

Effect of training on insulin binding to rat skeletal muscle sarcolemmal vesicles

1986 ◽  
Vol 250 (5) ◽  
pp. E570-E575
Author(s):  
G. K. Grimditch ◽  
R. J. Barnard ◽  
S. A. Kaplan ◽  
E. Sternlicht
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Insulin Binding ◽  
Whole Body ◽  
Rat Skeletal Muscle ◽  
Binding Studies ◽  
Muscle Enzyme ◽  
Intravenous Glucose ◽  
High Affinity

We examined the hypothesis that the exercise training-induced increase in skeletal muscle insulin sensitivity is mediated by adaptations in insulin binding to sarcolemmal (SL) insulin receptors. Insulin binding studies were performed on rat skeletal muscle SL isolated from control and trained rats. No significant differences were noted between groups in body weight or fat. An intravenous glucose tolerance test showed an increase in whole-body insulin sensitivity with training, and specific D-glucose transport studies on isolated SL vesicles indicated that this was due in part to adaptations in skeletal muscle. Enzyme marker analyses revealed no differences in yield, purity, or contamination of SL membranes between the two groups. Scatchard analyses indicated no significant differences in the number of insulin binding sites per milligram SL protein on the high-affinity (15.0 +/- 4.1 vs. 18.1 +/- 6.4 X 10(9)) or on the low-affinity portions (925 +/- 80 vs. 884 +/- 106 X 10(9)) of the curves. The association constants of the high-affinity (0.764 +/- 0.154 vs. 0.685 +/- 0.264 X 10(9) M-1) and of the low affinity sites (0.0096 +/- 0.0012 vs. 0.0102 +/- 0.0012 X 10(9) M-1) also were similar. These results do not support the hypothesis that the increased sensitivity to insulin after exercise training is due to changes in SL insulin receptor binding.

scholarly journals Carbohydrate Restriction with or without Exercise Training Improves Blood Pressure and Insulin Sensitivity in Overweight Women

Healthcare ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 637
Author(s):  
Shengyan Sun ◽  
Zhaowei Kong ◽  
Qingde Shi ◽  
Haifeng Zhang ◽  
On-Kei Lei ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Fasting Glucose ◽  
Training Group ◽  
Moderate Intensity ◽  
Cardiometabolic Health ◽  
Carbohydrate Restriction ◽  
Obese Women ◽  
Low Carbohydrate Diet

Objective: The purpose of this study was to evaluate the effects of a 4-week low-carbohydrate diet (LC) with or without exercise training on cardiometabolic health-related profiles in overweight/obese women. Methods: Fifty overweight/obese Chinese women (age: 22.2 ± 3.3 years, body mass index (BMI): 25.1 ± 3.1 kg·m−2) were randomized to either a LC control group (LC-CON, n = 16), a LC and high-intensity interval training group (LC-HIIT, n = 17), or a LC and moderate-intensity continuous training group (LC-MICT, n = 17). All groups consumed LC for 4 weeks, while the LC-HIIT and LC-MICT groups followed an additional five sessions of HIIT (10 × 6 s cycling sprints and 9 s rest intervals, 2.5 min in total) or MICT (cycling continuously at 50–60% of peak oxygen uptake (VO2peak) for 30 min) weekly. Blood pressure, fasting glucose, insulin sensitivity, and several metabolic or appetite regulating hormones were measured before and after intervention. Results: Significant reductions in body weight (− ~2.5 kg, p < 0.001, η2 = 0.772) and BMI (− ~1 unit, p < 0.001, η2 = 0.782) were found in all groups. Systolic blood pressure was reduced by 5–6 mmHg (p < 0.001, η2 = 0.370); fasting insulin, leptin, and ghrelin levels were also significantly decreased (p < 0.05), while insulin sensitivity was improved. However, there were no significant changes in fasting glucose, glucagon, and gastric inhibitory peptide levels. Furthermore, no group differences were found among the three groups, suggesting that extra training (i.e., LC-HIIT and LC-MICT) failed to trigger additional effects on these cardiometabolic profiles. Conclusions: The short-term carbohydrate restriction diet caused significant weight loss and improved blood pressure and insulin sensitivity in the overweight/obese women, although the combination with exercise training had no additional benefits on the examined cardiometabolic profiles. Moreover, the long-term safety and effectiveness of LC needs further study.

Hypoxic pressor response, cardiac size, and natriuretic peptides are modified by long-term intermittent hypoxia

1999 ◽  
Vol 87 (6) ◽  
pp. 2025-2031 ◽  
Author(s):  
Holger Kraiczi ◽  
Jarkko Magga ◽  
Xiang Ying Sun ◽  
Heikki Ruskoaho ◽  
Xiaohe Zhao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Body Weight ◽  
Atrial Natriuretic Peptide ◽  
Right Ventricular ◽  
Natriuretic Peptide ◽  
Intermittent Hypoxia ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

We investigated whether the effect of long-term intermittent hypoxia (LTIH) on cardiovascular function may be modified by preexisting genetic traits. To induce LTIH experimentally, cycles of 90-s hypoxia (nadir 6%) followed by 90-s normoxia were applied to six Wistar-Kyoto and six spontaneously hypertensive rats during 8 h daily. Comparison with the same number of control animals after 70 days revealed no alteration of intra-arterial blood pressure or heart rate. Blood pressure responsiveness to a brief hypoxic stimulus was enhanced in the LTIH animals, regardless of strain, whereas the hypoxia-induced increase in heart rate was abolished. In the spontaneously hypertensive but not the Wistar-Kyoto rats, LTIH increased left ventricular weight-to-body weight ratio and content of atrial natriuretic peptide mRNA. Expression of B-type natriuretic peptide was unchanged (Northern blot). Slightly increased right ventricular weight-to-body weight ratios in the LTIH animals were associated with higher right ventricular atrial natriuretic peptide and B-type natriuretic peptide mRNA amounts. Consequently, the effects of LTIH on different components of cardiovascular function appear incompletely related to each other and differentially influenced by constitutional traits.

scholarly journals Lipid Metabolism Links Nutrient-Exercise Timing to Insulin Sensitivity in Men Classified as Overweight or Obese

2019 ◽  
Vol 105 (3) ◽  
pp. 660-676 ◽  
Author(s):  
Robert M Edinburgh ◽  
Helen E Bradley ◽  
Nurul-Fadhilah Abdullah ◽  
Scott L Robinson ◽  
Oliver J Chrzanowski-Smith ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Whole Body ◽  
Moderate Intensity ◽  
Type I ◽  
Training Study ◽  
Exercise Timing ◽  
Lipid Utilization ◽  
Acute Study ◽  
Intramuscular Lipid

Abstract Context Pre-exercise nutrient availability alters acute metabolic responses to exercise, which could modulate training responsiveness. Objective To assess acute and chronic effects of exercise performed before versus after nutrient ingestion on whole-body and intramuscular lipid utilization and postprandial glucose metabolism. Design (1) Acute, randomized, crossover design (Acute Study); (2) 6-week, randomized, controlled design (Training Study). Setting General community. Participants Men with overweight/obesity (mean ± standard deviation, body mass index: 30.2 ± 3.5 kg⋅m-2 for Acute Study, 30.9 ± 4.5 kg⋅m-2 for Training Study). Interventions Moderate-intensity cycling performed before versus after mixed-macronutrient breakfast (Acute Study) or carbohydrate (Training Study) ingestion. Results Acute Study—exercise before versus after breakfast consumption increased net intramuscular lipid utilization in type I (net change: –3.44 ± 2.63% versus 1.44 ± 4.18% area lipid staining, P &lt; 0.01) and type II fibers (–1.89 ± 2.48% versus 1.83 ± 1.92% area lipid staining, P &lt; 0.05). Training Study—postprandial glycemia was not differentially affected by 6 weeks of exercise training performed before versus after carbohydrate intake (P &gt; 0.05). However, postprandial insulinemia was reduced with exercise training performed before but not after carbohydrate ingestion (P = 0.03). This resulted in increased oral glucose insulin sensitivity (25 ± 38 vs –21 ± 32 mL⋅min-1⋅m-2; P = 0.01), associated with increased lipid utilization during exercise (r = 0.50, P = 0.02). Regular exercise before nutrient provision also augmented remodeling of skeletal muscle phospholipids and protein content of the glucose transport protein GLUT4 (P &lt; 0.05). Conclusions Experiments investigating exercise training and metabolic health should consider nutrient-exercise timing, and exercise performed before versus after nutrient intake (ie, in the fasted state) may exert beneficial effects on lipid utilization and reduce postprandial insulinemia.

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