The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused studies were also performed in tissues from ob/ob and db/db mice. We document that T2D, both early and late onset, are characterized by reduced muscle expression of genes involved in branched-chain amino acids (BCAA) metabolism. Weighted Co-expression Networks Analysis provided support to idea that the BCAA genes are relevant in the pathophysiology of type 2 diabetes, and that mitochondrial BCAA management is impaired in skeletal muscle from T2D patients. In diabetic mice model we detected alterations in skeletal muscle proteins involved in BCAA metabolism but not in obese mice. Metabolomic analysis revealed increased levels of branched-chain keto acids (BCKA), and BCAA in plasma of T2D patients, which may result from the disruption of muscle BCAA management. Our data support the view that inhibition of genes involved in BCAA handling in skeletal muscle takes place as part of the pathophysiology of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes.

Background: Fetuin-A is a hepatokine linked to the development of insulin resistance. The purpose of this study was to determine if 60 days head-down-tilt (HDT) bed rest increased circulating fetuin-A and if it was linked to whole body insulin sensitivity (IS). Additionally, we examined whether reactive jump training (RJT) could alleviate the metabolic changes associated with bed rest. Methods: 23 young men (29 ± 6 years, 181 ± 6 cm, 77 ± 7 kg) were randomized to a control (CTRL, n = 11) or RJT group (JUMP, n = 12) and exposed to 60 days of bed rest. Before and after bed rest, body composition and V. O 2peak were measured and an oral glucose tolerance test was performed to estimate IS. Circulating lipids and fetuin-A were measured in fasting serum. Results: Body weight, lean mass, and V. O 2peak decreased in both groups following bed rest, with greater reductions in CTRL (p < 0.05). There was a main effect of time, but not the RJT intervention, for the increase in fetuin-A, triglycerides (TG), area under the curve for glucose (AUCG) and insulin (AUCI), and the decrease in Matsuda and tissue-specific IS (p < 0.05). Fetuin-A increased in participants who became less insulin sensitive (p = 0.019). In this subgroup, liver IS and adipose IS decreased (p < 0.05), while muscle IS was unchanged. In a subgroup, where IS did not decrease, fetuin-A did not change. Liver IS increased (p = 0.012), while muscle and adipose tissue IS remained unchanged. Conclusions: In this study, we report an increase in circulating fetuin-A following 60 days of bed rest, concomitant with reduced IS, which could not be mitigated by RJT. The amount of fetuin-A released from the liver may be an important determinant of changes in whole body IS. In this regard, it may also be a useful biomarker of individual variation due to inactivity or lifestyle interventions.

A series of studies were conducted to test the hypothesis that compression socks (uniform or graduated compression) worn after exercise mitigate exercise-induced pain. Fifty-nine (59) participants took part in three separate exercise protocols to induce a degree of muscle soreness from low to severe. Participants wore either ankle height socks with no compression (NoCo), knee height socks with uniform (UNI) or graduated compression (GRAD) for 8 h/day following exercise. Before, immediately after and during recovery, we measured muscle strength, flexibility and the perception of pain. The three exercise protocols were as follows. (1) Hike: compared the effects of GRAD and NoCo socks following a 10-km treadmill hike with a 1000 m ascent and descent. (2) Trail Run: compared the effect of GRAD and UNI following a 14-km trail run with 250 m ascent and descent. (3) Calf Exercise: compared the effect of GRAD and UNI socks with a predominately eccentric calf exercise. GRAD socks significantly mitigated the perception of calf pain compared to NoCo (Hike). The UNI socks were superior to the GRAD socks in mitigating the perception of pain during recovery in the Trail Run. No statistical difference was noted between UNI and GRAD socks after the Calf Exercise. Compression socks mitigated the perception of calf muscle pain (Hike trial), with UNI providing more benefit compared to GRAD socks (Trail Run trial). No differences between the UNI and GRAD socks were observed in the Calf Exercise trial. Compression socks aid in the perception of recovery following low to moderate pain from delayed onset muscle soreness.

No abstract

No abstract