Muscle hypertrophic effect of inhaled beta2 -agonist is associated with augmented insulin-stimulated whole-body glucose disposal in young men.

Rodent studies highlight enhancement of glucose tolerance and insulin sensitivity as potential clinically relevant effects of chronic beta2 -agonist treatment. However, the doses administered to rodents are not comparable with the therapeutic doses used for humans. Thus, we investigated the physiological effects of prolonged beta2 -agonist treatment at inhaled doses resembling those used in respiratory diseases on insulin-stimulated whole-body glucose disposal and putative mechanisms in skeletal muscle and adipose tissue of healthy men. Utilizing a randomized placebo-controlled parallel-group design, we assigned 21 healthy men to 4 weeks daily inhalation of terbutaline (TER; 4 mg × day-1 , n = 13) or placebo (PLA, n = 8). Before and after treatments, we assessed subjects' whole-body insulin-stimulated glucose disposal and body composition, and collected vastus lateralis muscle and abdominal adipose tissue biopsies. Glucose infusion rate increased by 27% (95% CI: 80 to 238 mg × min-1 , P = 0.001) in TER, whereas no significant changes occurred in PLA (95% CI: -37 to 195 mg × min-1 , P = 0.154). GLUT4 content in muscle or adipose tissue did not change, nor did hexokinase II content or markers of mitochondrial volume in muscle. Change in lean mass was associated with change in glucose infusion rate in TER (r = 0.59, P = 0.03). Beta2 -agonist treatment in close-to-therapeutic doses may augment whole-body insulin-stimulated glucose disposal in healthy young men and part of the change is likely to be explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2 -agonists for improving insulin sensitivity. KEY POINTS: While studies in rodents have highlighted beta2 -agonists as a means to augment insulin sensitivity, these studies utilized beta2 -agonists at doses inapplicable to humans. Herein we show that a 4-week treatment period with daily therapeutic inhalation of beta2 -agonist increases insulin-stimulated whole-body glucose disposal in young healthy lean men. This effect was associated with an increase of lean mass but not with changes in GLUT4 and hexokinase II or basal glycogen content in skeletal muscle nor GLUT4 content in abdominal adipose tissue. These findings suggest that the enhanced insulin-stimulated whole-body glucose disposal induced by a period of beta2 -agonist treatment in humans, at least in part, is attributed to muscle hypertrophy. Our observations extend findings in rodents and highlight the therapeutic potential of beta2 -agonists to enhance the capacity for glucose disposal and whole-body insulin sensitivity, providing important knowledge with potential application in insulin resistance.

Hypertension is associated with blunted NO-mediated leg vasodilator responsiveness that is reversed by high-intensity training in postmenopausal women.

The menopausal transition is associated with increased prevalence of hypertension, and in time, postmenopausal women (PMW) will exhibit a cardiovascular disease risk score similar to male counterparts. Hypertension is associated with vascular dysfunction, but whether hypertensive (HYP) PMW have blunted nitric oxide (NO)-mediated leg vasodilator responsiveness and whether this is reversible by high-intensity training (HIT) is unknown. To address these questions, we examined the leg vascular conductance (LVC) in response to femoral infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) and skeletal muscle markers of oxidative stress and NO bioavailability before and after HIT in PMW [12.9 ± 6.0 (means ± SD) years since last menstrual cycle]. We hypothesized that ACh- and SNP-induced LVC responsiveness was reduced in hypertensive compared with normotensive (NORM) PMW and that 10 wk of HIT would reverse the blunted LVC response and decrease blood pressure (BP). Nine hypertensive (HYP (clinical systolic/diastolic BP, 149 ± 11/91 ± 83 mmHg) and eight normotensive (NORM (122 ± 13/75 ± 8 mmHg) PMW completed 10 wk of biweekly small-sided floorball training (4-5 × 3-5 min interspersed by 1-3-min rest periods). Before training, the SNP-induced change in LVC was lower (P < 0.05) in HYP compared with in NORM. With training, the ACh- and SNP-induced change in LVC at maximal infusion rates, i.e., 100 and 6 µg·min-1·kg leg mass-1, respectively, improved (P < 0.05) in HYP only. Furthermore, training decreased (P < 0.05) clinical systolic/diastolic BP (-15 ± 11/-9 ± 7 mmHg) in HYP and systolic BP (-10 ± 9 mmHg) in NORM. Thus, the SNP-mediated LVC responsiveness was blunted in HYP PMW and reversed by a period of HIT that was associated with a marked decrease in clinical BP.

Efficacy of 10-20-30 training versus moderate-intensity continuous training on HbA1c, body composition and maximum oxygen uptake in male patients with type 2 diabetes: A randomized controlled trial.

AIM: To compare the efficacy of 10-20-30 training versus moderate-intensity continuous training (MICT) on HbA1c, body composition and maximum oxygen uptake (V˙O2 max) in male patients with type 2 diabetes (T2D). MATERIALS AND METHODS: Fifty-one male participants with T2D were randomly assigned (1:1) to a 10-20-30 (N = 26) and a MICT (N = 25) training group. Interventions consisted of supervised cycling three times weekly for 10 weeks, lasting 29 minutes (10-20-30) and 50 minutes (MICT) in a local non-clinical setting. The primary outcome was change in HbA1c from baseline to 10-week follow-up. RESULTS: Of 51 participants enrolled, 44 (mean age 61.0 ± 6.8 [mean ± SD] years, diagnosed 7.5 ± 5.8 years, baseline HbA1c 7.4% ± 1.3%) were included in the analysis. Training compliance was 84% and 86% in 10-20-30 and MICT, respectively. No adverse events occurred during the intervention. HbA1c decreased (P <0.001) by 0.5 (95% CI -0.72 to -0.21) percentage points with training in 10-20-30, with no change in MICT. The change in 10-20-30 was greater (P <0.05) than in MICT. Visceral fat mass decreased (P <0.05) only with 10-20-30 training, whereas total fat mass decreased (P <0.01) and V˙O2 max increased (P <0.01) with training in both groups. CONCLUSIONS: Ten weeks of 10-20-30 training was superior to MICT in lowering HbA1c, and only 10-20-30 training decreased visceral fat mass in patients with T2D. Furthermore, 10-20-30 training was as effective as MICT in reducing total fat mass and increasing V˙O2 max, despite a 42% lower training time commitment.

Increased prostacyclin formation after high-intensity interval training in late postmenopausal women.

PURPOSE: Aging impairs vascular function in women, with the largest detrimental effects occurring during the menopausal transition. Deficiency in the nitric oxide system has been suggested to be responsible for impairment in vascular function with aging, but recent observations suggest that the prostacyclin system, acting in redundancy with the nitric oxide system, may be of importance too. Improvement in vascular function is a hallmark of exercise training and we hypothesize that leg vascular function is improved by exercise training in late postmenopausal women, and that the underlying mechanism is increased endothelial formation of prostacyclin and responsiveness to prostacyclin by the vascular smooth muscle cells. METHOD: Femoral-arterial infusion of acetylcholine and epoprostenol was used to assess vascular function and prostacyclin release in ten late postmenopausal women (62 ± 7 years) before and after 10 weeks of high-intensity interval training (floorball conducted as small-sided games). RESULT: The training intervention increased fitness level (V̇O2max) by 7 ± 7% and reduced systolic and diastolic blood pressure by 10 ± 10 and 5 ± 6 mmHg, respectively. Leg vascular responsiveness to during acetylcholine and epoprostenol infusion was unchanged with training, whereas the release of prostacyclin during acetylcholine infusion increased by 125%. CONCLUSIONS: In late postmenopausal women, vascular function assessed by femoral-arterial infusion of acetylcholine was not improved after 10 weeks of floorball training, but acetylcholine-induced prostacyclin formation and blood pressure were substantially improved. It is possible that a longer training period could lead to improvements in vascular function and that the observed increase in prostacyclin formation is one of the initial underlying changes.

Skeletal muscle proteins important for work capacity are altered with type 2 diabetes - Effect of 10-20-30 training.

The study examined whether men with type 2 diabetes exhibit lower expression of muscle proteins important for exercise capacity, and whether exercise training promotes adaptations in these proteins. In a cross-sectional and longitudinal study, conducted at the University of Copenhagen. Twelve men with type 2 diabetes (T2D) were compared to eleven nondiabetes counterparts (ND) matched for age and body composition (body fat percentage). T2D underwent 10 weeks of high-intensity interval exercise training (10-20-30 training). T2D had lower expression of SOD1 (-62%; p < 0.001) and ETC complex V (-34%; p = 0.003), along with higher expression of ETC complex IV (+66%; p = 0.007), MFN2 (+62%; p = 0.001), and DRP1 (+30%; p = 0.028) compared to ND. T2D had higher (p < 0.001) expression of Na+ /K+ α1 (+98%), α2 (+114%), and NHE1 (+144%) than ND. In T2D, training increased exercise capacity (+9%; p < 0.001) as well as expression of SOD2 (+44%; p = 0.029), ETC complex II (+25%; p = 0.035), III (+52%; p = 0.041), IV (+23%; p = 0.005), and V (+21%; p = 0.035), CS activity (+32%; p = 0.006) as well as Na+ /K+ α1 (+24%; p = 0.034), Kir6.2 (+36%; p = 0.029), and MCT1 (+20%; p = 0.007). Men with type 2 diabetes exhibited altered expression of a multitude of skeletal muscle proteins important for exercise capacity. Ten weeks of 10-20-30 training upregulated expression of muscle proteins regulating antioxidant defense, mitochondrial function, and ion handling while enhancing exercise capacity in men with type 2 diabetes.