The purpose this study was to examine the effects of caffeine ingestion on performance and energy expenditure (anaerobic and aerobic contribution) during a 4-km cycling time trial (TT) performed after a carbohydrate (CHO) availability-lowering exercise protocol. After preliminary and familiarization trials, seven amateur cyclists performed three 4-km cycling TT in a double-blind, randomized and crossover design. The trials were performed either after no previous exercise (CON), or after a CHO availability-lowering exercise protocol (DEP) performed in the previous evening, followed by either placebo (DEP-PLA) or 5 mg.kg−1 of caffeine intake (DEP-CAF) 1 hour before the trial. Performance was reduced (−2.1%) in DEP-PLA vs CON (421.0±12.3 vs 412.4±9.7 s). However, performance was restored in DEP-CAF (404.6±17.1 s) compared with DEP-PLA, while no differences were found between DEP-CAF and CON. The anaerobic contribution was increased in DEP-CAF compared with both DEP-PLA and CON (67.4±14.91, 47. 3±14.6 and 55.3±14.0 W, respectively), and this was more pronounced in the first 3 km of the trial. Similarly, total anaerobic work was higher in DEP-CAF than in the other conditions. The integrated electromyographic activity, plasma lactate concentration, oxygen uptake, aerobic contribution and total aerobic work were not different between the conditions. The reduction in performance associated with low CHO availability is reversed with caffeine ingestion due to a higher anaerobic contribution, suggesting that caffeine could access an anaerobic “reserve” that is not used under normal conditions.

We analyzed the influence of prior exercise designed to reduce predominantly muscle glycogen in either type I or II fibers on pacing and performance during a 4-km cycling time trial (TT). After preliminary and familiarization trials, in a randomized, repeated-measures crossover design, ten amateur cyclists performed: 1) an exercise designed to reduce glycogen of type I muscle fibers, followed by a 4-km TT (EX-FIB I); 2) an exercise designed to reduce glycogen of type II muscle fibers, followed by a 4-km TT (EX-FIB II) and; 3) a 4-km TT, without the prior exercise (CONT). The muscle-glycogen-reducing exercise in both EX-FIB I and EX-FIB II was performed in the evening, ∼12 h before the 4-km TT. Performance time was increased and power output (PO) was reduced in EX-FIB I (432.8±8.3 s and 204.9±10.9 W) and EX-FIB II (428.7±6.7 s and 207.5±9.1 W) compared to CONT (420.8±6.4 s and 218.4±9.3 W; P<0.01), without a difference between EX-FIB I and EX-FIB II (P>0.05). The PO was lower in EX-FIB I than in CONT at the beginning and middle of the trial (P<0.05). The mean aerobic contribution during EX-FIB I was also significantly lower than in CONT (P<0.05), but there was no difference between CONT and EX-FIB II or between EX-FIB I and EX-FIB II (P>0.05). The integrated electromyography was unchanged between conditions (P>0.05). Performance may have been impaired in EX-FIB I due a more conservative pacing at the beginning and middle, which was associated with a reduced aerobic contribution. In turn, the PO profile adopted in EX-FIB II was also reduced throughout the trial, but the impairment in performance may be attributed to a reduced glycolytic contribution (i.e. reduced lactate accumulation).

Population studies have shown an association between diabetic nephropathy (DN) and insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene (ACE in humans, Ace in mice). The aim was to evaluate the modulation of Ace copies number and diabetes mellitus (DM) on renal RAS and correlate it with indicators of kidney function. Increased number of copies of the Ace gene, associated with DM, induces renal dysfunction. The susceptibility to the development of DN in 3 copies of animals is associated with an imbalance in activity of RAS enzymes leading to increased synthesis of Ang II and Ang-(1–7). Increased concentration of renal Ang-(1–7) appears to potentiate the deleterious effects triggered by Ang II on kidney structure and function. Results also show increased bradykinin concentration in 3 copies diabetic group. Taken together, results indicate that the deleterious effects described in 3 copies diabetic group are, at least in part, due to a combination of factors not usually described in the literature. Thus, the data presented here show up innovative and contribute to understanding the complex mechanisms involved in the development of DN, in order to optimize the treatment of patients with this complication.

Previous studies from our laboratory have demonstrated that chronic diabetes in rats results in cardiomyopathy, associated with sympathetic nervous system (SNS) hyperactivity. On the other hand, it is well known that the beneficial cardiovascular effects of exercise training in diabetes are due in part to normalization of the sympathetic outflow and improvement in the responsiveness of the myocardium to autonomic stimulation. Recently, resistance training (RT) has been recognized as a useful therapeutic tool for the treatment of chronic diseases and similar to aerobic exercise, has been reported to improve metabolic profile and body composition. Therefore, the aim of this study was to evaluate the effect of moderate-intensity RT on circulating and cardiac catecholamines concentration, to understand whether this type of exercise is also associated with cardiovascular protection. Wistar rats (3 months old) were randomized into: control (C), diabetic (D), diabetic + RPT (DR) and diabetic + APT (DA). Animals were made diabetic with a single tail injection of streptozotocin (STZ, 50 mg/Kg). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load, and moderate aerobic training was performed on a treadmill (5 days/week, 8 weeks). Diabetes significantly increased plasma concentration of adrenaline (D: 5.3 ± 1.0 vs. C: 4.1 ± 0.6 ng/mL) and noradrenaline (D: 14.5 ± 0.2 vs. C: 3.1± 0.8 ng/mL), and both exercise modalities induced a significant reduction of them: adrenaline (DR: 1.1 ± 0.3; DA: 0.7 ± 0.16 vs. D: 5.3 ± 1.0 ng/mL) and noradrenaline (DR: 1.0 ± 0.2; DA: 0.7 ± 0.1 vs. D: 14.5 ± 0.2 ng/mL). Cardiac concentration of noradrenaline was also increased in diabetic group (D: 62 ± 7 vs. CS: 34 ± 6 pg/g) and only aerobic exercise was capable to reduce its concentration in heart tissue (DA: 30 ± 6 vs. D: 62 ± 7; DR: 55 ± 7 pg/g). The results from the present study show for the first time additional beneficial effects of RT on modulating SNS activity in diabetes. Moreover, considering that RT does not modulate cardiac catecholaminergic secretion, it also highlights the importance of aerobic training in diabetes treatment. Financial Support: FAPESP, CAPES, CNPq

Overactivity of the intrarenal renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. Our group has already demonstrated that aerobic exercise reduces kidney angiotensin II levels and attenuates renal dysfunction under concurrence of diabetes and hypertension. Resistance training (RT) has recently been recognized as a useful therapeutic tool for the treatment chronic diseases and similar to aerobic exercise, has been reported to improve glycemic control. Therefore, the aim of this study was to evaluate the effect of RT on renal function and RAS in diabetic animals, to understand whether this type of exercise is also associated with renoprotection. Wistar rats (3 months old) were randomized into: sedentary control (SC); trained control (TC); sedentary diabetic (SD) and trained diabetic (TD). Animals were made diabetic with a single tail injection of streptozotocin (STZ, 50 mg/Kg). RT was performed on an 110-cm ladder (8 ladder climbs, once/day, 5 days/week, 8 weeks), carrying a load of 50-80% body weight (BW) appended to the tail. At week 8, 24 hr urine volume and albuminuria were evaluated. Kidney was excised and ACE and ACE2 activities were determined (ZPhe-HL and 7-Mca-APK(Dnp), respectively) (Two way ANOVA + Tukey test; P<0.05). RT significantly reduced blood glucose (TD = 449 ± 17 vs. SD = 572 ± 18 mg/dL) and attenuated BW loss of diabetic animals. DM reduced renal ACE activity in sedentary and trained groups (SD = 3.72 ± 0.48, TD = 3.85 ± 0.40 vs. SC = 9.2 ± 0.59 nmol/min/mg), while RT reduced enzyme activity only in control group (TC = 5.14 ± 0.26 vs. SC = 9.2 ± 0.59 nmol/min/mg). RT reduced renal ACE2 in the control group compared to the others (TC = 0.05 ± 0.0001 vs. SC = 0.09 ± 0.004, SD = 0.09 ± 0.003, TD = 0.10 ± 0.002 μM/min/mg), with no effect of diabetes on enzyme activity. RT improved renal function, decreasing urinary volume and albuminuria (DT = 4.13 ± 0.84 vs. SD = 11 ± 2.11 mg/24h) in DT group. The results from the present study show that RT is strongly associated with renoprotection in an experimental model of diabetic nephropathy. Moreover, results show that this improvement on renal function is modulated by other pathways apart from ACE and ACE2 converting enzymes. Financial Support: FAPESP, CAPES, CNPq.

Prior study of our group shown that previous aerobic exercise training improved the damage caused by diabetes mellitus on renal and cardiovascular system. Resistance exercise training, also known as strength training, is traditionally performed to gain muscle mass; however, it is not clear whether this type of exercise modulates renal system. Additionally, it is also unknown whether previous resistance exercise training can potentially influence the kidney and skeletal muscle. Wistar rats were submitted to resistance exercise training in an apparatus developed especially to this type of exercise (8 - 12 climbs/day, 5 days/week, 12 weeks). Previous resistance exercise trained group (PTD) performed for 4 weeks before the establishment of the disease and after this period they were followed by 8 weeks of resistance exercise training. Additional trained groups such as trained diabetic (TD) and trained control (TC) groups were followed by 8 weeks of resistance exercise training. Control groups were also followed (control - C, diabetes - D). We have found that PTD suppressed abnormalities linked to renal system such as, water consumption and amount of urine PTD=71mL vs. DT=127mL vs. D=138mL (measured during metabolic cage period), as well as attenuated proteinuria and kidney weight. Regarding to skeletal muscle, PTD group had increased muscle weight (extensor digitorium longus - EDL; C=192mg, D=116mg, TD=106mg and PTD=126mg; Tibialis anterior, C=780mg, D=496mg, DT=450mg and PTD=535mg); we also found a great muscle force level in the PTD group (C=573g, CT=1037, D=414g, TD=737g and PTD=825g), suggesting a protective effect of previous exercise in this group. PTEN was suppressed in PTD group and Akt and 4EBP1 (upstream and downstream of mTOR) were activated in PTD group, measured by western blot. These data suggest that, resistance exercise performed prior the establishment of the diabetes mellitus can protect kidney from diabetic nephropathy and skeletal muscle from atrophy. The mechanisms by which kidney and skeletal muscle have been improved are linked to mTOR signaling pathway. Further studies will be performed to confirm the potential involvement of this signaling pathway. Support: FAPESP, CAPES, CNPq.