Impact of exercise-nutritional state interactions in patients with type 2 diabetes

Introduction This study examines the role of nutritional status during exercise training in patients with type 2 diabetes mellitus by investigating the effect of endurance-type exercise training in the fasted versus the fed state on clinical outcome measures, glycemic control, and skeletal muscle characteristics in male type 2 diabetes patients. Methods Twenty-five male patients (glycated hemoglobin (HbA1c), 57 ± 3 mmol·mol−1 (7.4% ± 0.3%)) participated in a randomized 12-wk supervised endurance-type exercise intervention, with exercise being performed in an overnight-fasted state (n = 13) or after consuming breakfast (n = 12). Patients were evaluated for glycemic control, blood lipid profiles, body composition and physical fitness, and skeletal muscle gene expression. Results Exercise training was well tolerated without any incident of hypoglycemia. Exercise training significantly decreased whole-body fat mass (−1.6 kg) and increased high-density lipoprotein concentrations (+2 mg·dL−1), physical fitness (+1.7 mL·min−1·kg−1), and fat oxidation during exercise in both groups (PTIME 0.05). HbA1c concentrations significantly decreased after exercise training (PTIME < 0.001), with a significant greater reduction after consuming breakfast (−0.30% ± 0.06%) compared with fasted state (−0.08% ± 0.06%; mean difference, 0.21%; PTIME × GROUP = 0.016). No interaction effects were observed for skeletal muscle genes related to lipid metabolism or oxidative capacity. Conclusions Endurance-type exercise training in the fasted or fed state do not differ in their efficacy to reduce fat mass, increase fat oxidation capacity, and increase cardiorespiratory fitness and high-density lipoprotein concentrations or their risk of hypoglycemia in male patients with type 2 diabetes. HbA1c seems to be improved more with exercise performed in the postprandial compared with the postabsorptive state

Satellite cells in human skeletal muscle plasticity

Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models

Amplification of a Zygosaccharomyces bailii DNA Segment in Wine Yeast Genomes by Extrachromosomal Circular DNA Formation

We recently described the presence of large chromosomal segments resulting from independent horizontal gene transfer (HGT) events in the genome of Saccharomyces cerevisiae strains, mostly of wine origin. We report here evidence for the amplification of one of these segments, a 17 kb DNA segment from Zygosaccharomyces bailii, in the genome of S. cerevisiae strains. The copy number, organization and location of this region differ considerably between strains, indicating that the insertions are independent and that they are post-HGT events. We identified eight different forms in 28 S. cerevisiae strains, mostly of wine origin, with up to four different copies in a single strain. The organization of these forms and the identification of an autonomously replicating sequence functional in S. cerevisiae, strongly suggest that an extrachromosomal circular DNA (eccDNA) molecule serves as an intermediate in the amplification of the Z. bailii region in yeast genomes. We found little or no sequence similarity at the breakpoint regions, suggesting that the insertions may be mediated by nonhomologous recombination. The diversity between these regions in S. cerevisiae represents roughly one third the divergence among the genomes of wine strains, which confirms the recent origin of this event, posterior to the start of wine strain expansion. This is the first report of a circle-based mechanism for the expansion of a DNA segment, mediated by nonhomologous recombination, in natural yeast populations

Exercise therapy in Type 2 diabetes

Structured exercise is considered an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in Type 2 diabetes. Current clinical guidelines acknowledge the therapeutic strength of exercise intervention. This paper reviews the wide pathophysiological problems associated with Type 2 diabetes and discusses the benefits of exercise therapy on phenotype characteristics, glycemic control and cardiovascular risk profile in Type 2 diabetes patients. Based on the currently available literature, it is concluded that Type 2 diabetes patients should be stimulated to participate in specifically designed exercise intervention programs. More attention should be paid to cardiovascular and musculoskeletal deconditioning as well as motivational factors to improve long-term treatment adherence and clinical efficacy. More clinical research is warranted to establish the efficacy of exercise intervention in a more differentiated approach for Type 2 diabetes subpopulations within different stages of the disease and various levels of co-morbidity

Short term amino acid infusion improves protein balance in critically ill patients

INTRODUCTION: Evidence behind the recommendations for protein feeding during critical illness is weak. Mechanistic studies are needed to elucidate the effects of amino acid/protein supplementation on protein metabolism before larger clinical trials with higher protein feeding are initiated. METHODS: Here we study the effects of parenteral amino acid supplementation (equivalent to 1 g/kg/day) over 3 h on whole body protein turnover in critically ill patients in the ICU during the first week after admission. Patients were studied at baseline during ongoing nutrition and during extra amino acid supplementation. If the patient was still in the ICU 2-4 days later, these measurements were repeated. Protein kinetics were measured using continuous stable isotope labeled phenylalanine and tyrosine infusions. RESULTS: Thirteen patients were studied on the first study occasion only and 7 were studied twice. Parenteral amino acid supplementation significantly improved protein balance on both occasions; from median -4 to +7 mumol phenylalanine/kg/h (P = 0.001) on the first study day and from median 0 to +12 mumol phenylalanine/kg/h (P = 0.018) on the second study day. The more positive protein balance was attributed to an increased protein synthesis rate which reached statistical significance during the first measurement (from 58 to 65 mumol phenylalanine/kg/h; n = 13; P = 0.007) but not during the second measurement (from 58 to 69 mumol phenylalanine/kg/h; n = 7; P = 0.09). Amino acid oxidation rates, estimated by phenylalanine hydroxylation, did not increase during the 3 h amino acid infusion. A positive correlation (r = 0.80; P < 0.0001)) between total amino acids/protein given to the patient and whole body protein balance was observed. CONCLUSION: Extra parenteral amino acids infused over a 3 hour period improved whole body protein balance and did not increase amino acid oxidation rates in critically ill patients during the early phase (first week) of critical illness

Contribution of non-esterified fatty acids to mitogen-activated protein kinases activation in human skeletal muscle during endurance exercise

Mitogen-activated protein kinase (MAPK) pathways are activated in skeletal muscle during endurance exercise, but the upstream molecular events are incompletely resolved. As an increase in plasma nonesterified fatty acids (NEFA) is a common feature of long-lasting exercise, the authors tested the hypothesis that NEFA contribute to the activation of MAPK during endurance exercise. Acipimox was used before and during endurance exercise to prevent the elevation of plasma NEFA levels in healthy subjects and patients with diabetes. In 2 separate studies, healthy subjects cycled for 2 hr and patients with diabetes for 1 hr at 50% Wmax. In control conditions, plasma NEFA concentrations increased from 0.35 to 0.90 mM during exercise in healthy subjects and from 0.55 to 0.70 mM in patients with diabetes (p < .05). Phosphorylation states of extracellularly regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun NH2-terminal kinases (JNK) were significantly increased after exercise in the vastus lateralis in both groups. Acipimox blocked the increase in plasma NEFA concentrations and almost completely repressed any rise in ERK1/2 and p38 but not in JNK. In conclusion, the data support a role for plasma NEFA in the activation of p38 and ERK1/2 in skeletal-muscle tissue of healthy and diabetic subjects during endurance exercise. Further investigation will be required to determine the molecular link between NEFA and MAPK activation during exercise in human skeletal muscle.status: publishe

Myofibrillar protein synthesis rates are increased in chronically exercised skeletal muscle despite decreased anabolic signaling.

The molecular responses to acute resistance exercise are well characterized. However, how cellular signals change over time to modulate chronic adaptations to more prolonged exercise training is less well understood. We investigated anabolic signaling and muscle protein synthesis rates at several time points after acute and chronic eccentric loading. Adult rat tibialis anterior muscle was stimulated for six sets of ten repetitions, and the muscle was collected at 0&nbsp;h, 6&nbsp;h, 18&nbsp;h and 48&nbsp;h. In the last group of animals, 48&nbsp;h after the first exercise bout a second bout was conducted, and the muscle was collected 6&nbsp;h later (54&nbsp;h total). In a second experiment, rats were exposed to four exercise sessions over the course of 2 weeks. Anabolic signaling increased robustly 6&nbsp;h after the first bout returning to baseline between 18 and 48&nbsp;h. Interestingly, 6&nbsp;h after the second bout mTORC1 activity was significantly lower than following the first bout. In the chronically exercised rats, we found baseline anabolic signaling was decreased, whereas myofibrillar protein synthesis (MPS) was substantially increased, 48&nbsp;h after the last bout of exercise. The increase in MPS occurred in the absence of changes to muscle fiber size or mass. In conclusion, we find that anabolic signaling is already diminished after the second bout of acute resistance type exercise. Further, chronic exposure to resistance type exercise training results in decreased basal anabolic signaling but increased overall MPS rates

Co-ingesting milk fat with micellar casein does not affect postprandial protein handling in healthy older men

Background & aim: Dietary protein digestion and absorption plays an important role in modulating postprandial muscle protein synthesis. The impact of co-ingesting other macronutrients with dietary protein on protein digestion and absorption and the subsequent muscle protein synthetic response remains largely unexplored. This study investigated the impact of co-ingesting milk fat with micellar casein on dietary protein-derived amino acid appearance in the circulation and the subsequent postprandial muscle protein synthetic response in healthy older men. Methods: Twenty-four healthy, older males ( age: 65 ± 1 y, BMI: 25.7 ± 0.5 kg/m2 ) received a primed continuous infusion of L-[ring-2H5]-phenylalanine and L-[1–13C]-leucine and ingested 20 g intrinsically L-[1–13C]-phenylalanine and L-[1–13C]-leucine-labeled casein with ( PRO + FAT; n = 12 ) or without ( PRO; n = 12 ) 26.7 g milk fat. Plasma samples and muscle biopsies were collected in both the postabsorptive and postprandial state. Results: Release of dietary protein-derived phenylalanine into the circulation increased following protein ingestion ( P < 0.001 ) and tended to be higher in PRO compared with PRO + FAT ( Time × Treatment P = 0.076 ). No differences were observed in dietary protein-derived plasma phenylalanine availability ( 52 ± 2 vs 52 ± 3% in PRO vs PRO + FAT, respectively; P = 0.868 ). Myofibrillar protein synthesis rates did not differ between treatments, calculated using either the L-[ring-2H5]-phenylalanine ( 0.036 ± 0.003 vs 0.036 ± 0.004 %/h after PRO vs PRO + FAT, respectively; P = 0.933 ) or L-[1–13C]-leucine ( 0.051 ± 0.004 vs 0.046 ± 0.004 %/h, respectively; P = 0.480 ) tracer. In accordance, no differences were observed in myofibrillar protein-bound L-[1–13C]-phenylalanine enrichments between treatments ( 0.018 ± 0.002 vs 0.014 ± 0.001 MPE, respectively; P = 0.173 ). Conclusion: Co-ingesting milk fat with micellar casein does not impair protein-derived phenylalanine appearance in the circulation and does not modulate postprandial myofibrillar protein synthesis rates. Clinical Trial Registration Number: NCT01680146 ( http://www.clinicaltrials.gov/

Co-ingestion of a protein hydrolysate with or without additional leucine effectively reduces postprandial blood glucose excursions in type 2 diabetic men

This study examined postprandial plasma insulin and glucose responses after co-ingestion of an insulinotropic protein (Pro) hydrolysate with and without additional free leucine with a single bolus of carbohydrate (Cho). Male patients with long-standing Type 2 diabetes (n = 10) and healthy controls (n = 10) participated in 3 trials in which plasma glucose, insulin, and amino acid responses were determined after the ingestion of beverages of different composition (Cho: 0.7 g/kg carbohydrate, Cho+Pro: 0.7 g/kg carbohydrate with 0.3 g/kg protein hydrolysate, or Cho+Pro+Leu: 0.7 g/kg carbohydrate, 0.3 g/kg protein hydrolysate and 0.1 g/kg free leucine). Plasma insulin responses [expressed as area under the curve (AUC)] were 141 and 204% greater in patients with Type 2 diabetes and 66 and 221% greater in the controls in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P < 0.05). The concomitant plasma glucose responses were 15 and 12% lower in the patients with Type 2 diabetes and 92 and 97% lower in the control group in the Cho+Pro and Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P < 0.05). Plasma leucine concentrations correlated with the insulin response in all subjects (r = 0.43, P < 0.001). We conclude that co-ingestion of a protein hydrolysate with or without additional free leucine strongly augments the insulin response after ingestion of a single bolus of carbohydrate, thereby significantly reducing postprandial blood glucose excursions in patients with long-standing Type 2 diabetes. © 2006 American Society for Nutrition