Aerobic exercise training induces metabolic benefits in rats with metabolic syndrome independent of dietary changes

OBJECTIVES: We evaluated the effects of aerobic exercise training without dietary changes on cardiovascular and metabolic variables and on the expression of glucose transporter Type 4 in rats with metabolic syndrome. METHODS: Twenty male spontaneously hypertensive rats received monosodium glutamate during the neonatal period. The animals were allocated to the following groups: MS (sedentary metabolic syndrome), MS-T (trained on a treadmill for 1 hour/day, 5 days/week for 10 weeks), H (sedentary spontaneously hypertensive rats) and H-T (trained spontaneously hypertensive rats). The Lee index, blood pressure (tail-cuff system), insulin sensitivity (insulin tolerance test) and functional capacity were evaluated before and after 10 weeks of training. Glucose transporter Type 4 expression was analyzed using Western blotting. The data were compared using analysis of variance (ANOVA) (

The beneficial effects of exercise in rodents are preserved after detraining: a phenomenon unrelated to GLUT4 expression

<p>Abstract</p> <p>Background</p> <p>Although exercise training has well-known cardiorespiratory and metabolic benefits, low compliance with exercise training programs is a fact, and the harmful effects of physical detraining regarding these adaptations usually go unnoticed. We investigated the effects of exercise detraining on blood pressure, insulin sensitivity, and GLUT4 expression in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY).</p> <p>Methods</p> <p>Studied animals were randomized into sedentary, trained (treadmill running/5 days a week, 60 min/day for 10 weeks), 1 week of detraining, and 2 weeks of detraining. Blood pressure (tail-cuff system), insulin sensitivity (kITT), and GLUT4 (Western blot) in heart, gastrocnemius and white fat tissue were measured.</p> <p>Results</p> <p>Exercise training reduced blood pressure (19%), improved insulin sensitivity (24%), and increased GLUT4 in the heart (+34%); gastrocnemius (+36%) and fat (+22%) in SHR. In WKY no change in either blood pressure or insulin sensitivity were observed, but there was an increase in GLUT4 in the heart (+25%), gastrocnemius (+45%) and fat (+36%) induced by training. Both periods of detraining did not induce any change in neither blood pressure nor insulin sensitivity in SHR and WKY. One-week detraining reduced GLUT4 in SHR (heart: -28%; fat: -23%) and WKY (heart: -19%; fat: -22%); GLUT4 in the gastrocnemius was reduced after a 2-week detraining (SHR: -35%; WKY: -25%). There was a positive correlation between GLUT4 (gastrocnemius) and the maximal velocity in the exercise test (r = 0.60, p = 0.004).</p> <p>Conclusions</p> <p>The study findings show that in detraining, despite reversion of the enhanced GLUT4 expression, cardiorespiratory and metabolic beneficial effects of exercise are preserved.</p

Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

<p>Abstract</p> <p>Background</p> <p>The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored.</p> <p>Methods</p> <p>Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2) in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR) ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD) or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA) were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP) and heart rate variability (spectral analysis) one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting).</p> <p>Results</p> <p>Higher glycemia (p < 0.05) and lower mean AP were observed in diabetics <it>vs. </it>nondiabetics (p < 0.05). Heart rate was higher in renal-denervated hypertensive and lower in diabetic-hypertensive rats (384.8 ± 37, 431.3 ± 36, 316.2 ± 5, 363.8 ± 12 bpm in SHR, RD-SHR, STZ-SHR and RD-STZ-SHR, respectively). Heart rate variability was higher in renal-denervated diabetic-hypertensive rats (55.75 ± 25.21, 73.40 ± 53.30, 148.4 ± 93 in RD-SHR, STZ-SHR- and RD-STZ-SHR, respectively, p < 0.05), as well as the LF component of AP variability (1.62 ± 0.9, 2.12 ± 0.9, 7.38 ± 6.5 in RD-SHR, STZ-SHR and RD-STZ-SHR, respectively, p < 0.05). GLUT2 renal content was higher in all groups <it>vs</it>. SHR.</p> <p>Conclusions</p> <p>Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.</p

Diabetes Modulates MicroRNAs 29b-3p, 29c-3p, 199a-5p and 532-3p Expression in Muscle: Possible Role in GLUT4 and HK2 Repression

The reduced expression of solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) and hexokinase-2 (HK2) in skeletal muscle participates in insulin resistance of diabetes mellitus (DM). MicroRNAs (miRNAs) have emerged as important modulators of mRNA/protein expression, but their role in DM is unclear. We investigated miRNAs hypothetically involved in GLUT4/HK2 expression in soleus muscle of type 1 diabetes-like rats. In silico analysis revealed 651 miRNAs predicted to regulate solute carrier family 2 member 4 (Slc2a4) mRNA, several of them also predicted to regulate Hk2 mRNA, and 16 miRNAs were selected for quantification. Diabetes reduced Slc2a4/GLUT4 and Hk2/HK2 expression (50–77%), upregulated miR-29b-3p and miR-29c-3p (50–100%), and downregulated miR-93-5p, miR-150-5p, miR-199a-5p, miR-345-3p, and miR-532-3p (~30%) expression. Besides, GLUT4 and HK2 proteins correlated (P &lt; 0.05) negatively with miR-29b-3p and miR-29c-3p and positively with miR-199a-5p and miR-532-3p, suggesting that these miRNAs could be markers of alterations in GLUT4 and HK2 expression. Additionally, diabetes increased the nuclear factor kappa B subunit 1 protein (p50) expression, a repressor of Slc2a4, which was also predicted as a target for miR-199a-5p and miR-532-3p. Correlations were also detected between these miRNAs and blood glucose, 24-h glycosuria and plasma fructosamine, and insulin therapy reversed most of the alterations. In sum, we report that diabetes altered miR-29b-3p, miR-29c-3p, miR-199a-5p and miR-532-3p expression in muscle of male rats, where their predicted targets Slc2a4/GLUT4 and Hk2/HK2 are repressed. These data shed light on these miRNAs as a markers of impaired skeletal muscle glucose disposal, and, consequently, glycemic control in diabetes

GLUT4 content decreases along with insulin resistance and high levels of inflammatory markers in rats with metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome is characterized by insulin resistance, which is closely related to GLUT4 content in insulin-sensitive tissues. Thus, we evaluated the GLUT4 expression, insulin resistance and inflammation, characteristics of the metabolic syndrome, in an experimental model.</p> <p>Methods</p> <p>Spontaneously hypertensive neonate rats (18/group) were treated with monosodium glutamate (MetS) during 9 days, and compared with Wistar-Kyoto (C) and saline-treated SHR (H). Blood pressure (BP) and lipid levels, C-reactive protein (CRP), interleukin 6 (IL-6), TNF-α and adiponectin were evaluated. GLUT4 protein was analysed in the heart, white adipose tissue and gastrocnemius. Studies were performed at 3 (3-mo), 6 (6-mo) and 9 (9-mo) months of age.</p> <p>Results</p> <p>MetS rats were more insulin resistant (p<0.001, all ages) and had higher BP (3-mo: p<0.001, 6-mo: p = 0.001, 9-mo: p = 0.015) as compared to C. At 6 months, CRP, IL-6 and TNF-α were higher (p<0.001, all comparisons) in MetS rats <it>vs</it> H, but adiponectin was lower in MetS at 9 months (MetS: 32 ± 2, H: 42 ± 2, C: 45 ± 2 pg/mL; p<0.001). GLUT4 protein was reduced in MetS as compared to C rats at 3, 6 and 9-mo, respectively (Heart: 54%, 50% and 57%; Gastrocnemius: 37%, 56% and 50%; Adipose tissue: 69%, 61% and 69%).</p> <p>Conclusions</p> <p>MSG-treated SHR presented all metabolic syndrome characteristics, as well as reduced GLUT4 content, which must play a key role in the impaired glycemic homeostasis of the metabolic syndrome.</p