Improvement in coronary endothelial function is independently associated with a slowed progression of coronary artery calcification in type 2 diabetes mellitus.

Aims: To examine a relationship between alterations of structure and function of the arterial wall in response to glucose-lowering therapy in type 2 diabetes mellitus (DM) after a 1-year follow-up (FU).

Methods And Results: In DM (n = 22) and in healthy controls (n = 17), coronary artery calcification (CAC) was assessed with electron beam tomography and carotid intima-media thickness (IMT) with ultrasound, whereas coronary function was determined with positron emission tomography-measured myocardial blood flow (MBF) at rest, during cold pressor testing (CPT), and during adenosine stimulation at baseline and after FU. The decrease in plasma glucose in DM after a mean FU of 14 +/- 1.

Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus.

Purpose: To determine the relationship between carotid intima-media thickness (IMT), coronary artery calcification (CAC), and myocardial blood flow (MBF) at rest and during vasomotor stress in type 2 diabetes mellitus (DM).

Methods: In 68 individuals, carotid IMT was measured using high-resolution vascular ultrasound, while the presence of CAC was determined with electron beam tomography (EBT). Global and regional MBF was determined in milliliters per gram per minute with (13)N-ammonia and positron emission tomography (PET) at rest, during cold pressor testing (CPT), and during adenosine (ADO) stimulation.

Blood flow restriction during low-intensity resistance exercise increases S6K1 phosphorylation and muscle protein synthesis.

Low-intensity resistance exercise training combined with blood flow restriction (REFR) increases muscle size and strength as much as conventional resistance exercise with high loads. However, the cellular mechanism(s) underlying the hypertrophy and strength gains induced by REFR are unknown. We have recently shown that both the mammalian target of rapamycin (mTOR) signaling pathway and muscle protein synthesis (MPS) were stimulated after an acute bout of high-intensity resistance exercise in humans.

Nutrient signalling in the regulation of human muscle protein synthesis.

The mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) are important nutrient- and energy-sensing and signalling proteins in skeletal muscle. AMPK activation decreases muscle protein synthesis by inhibiting mTOR signalling to regulatory proteins associated with translation initiation and elongation. On the other hand, essential amino acids (leucine in particular) and insulin stimulate mTOR signalling and protein synthesis.

Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling.

Muscle protein metabolism is resistant to insulin's anabolic effect in healthy older subjects. This is associated with reduced insulin vasodilation. We hypothesized that aerobic exercise restores muscle protein anabolism in response to insulin by improving vasodilation in older subjects.

Assessment of intra- and interobserver reproducibility of rest and cold pressor test-stimulated myocardial blood flow with (13)N-ammonia and PET.

Purpose: We investigated the intraobserver reproducibility of myocardial blood flow (MBF) measurements with PET at rest and during cold pressor test (CPT), and the interobserver agreement.

Methods: Twenty normal volunteers were studied. Using (13)N-ammonia, MBF was measured at rest and during CPT and measurement was repeated in a 1-day session (short-term reproducibility; SR).

Basal muscle intracellular amino acid kinetics in women and men.

Sexual dimorphism in skeletal muscle mass is apparent, with men having more muscle mass and larger individual muscle cells. However, no sex-based differences have been detected in blood forearm phenylalanine turnover, although whole body leucine oxidation has been reported to be greater in men than in women. We hypothesized that sex differences in intracellular amino acid turnover may account for these discrepancies, with men having a higher intracellular turnover than women.

Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle.

Resistance exercise is a potent stimulator of muscle protein synthesis and muscle cell growth, with the increase in protein synthesis being detected within 2-3 h post-exercise and remaining elevated for up to 48 h. However, during exercise, muscle protein synthesis is inhibited. An increase in AMP-activated protein kinase (AMPK) activity has recently been shown to decrease mammalian target of rapamycin (mTOR) signalling to key regulators of translation initiation.

Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability.

Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable-isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in one leg at low (LD, 0.

Skeletal muscle protein anabolic response to increased energy and insulin is preserved in poorly controlled type 2 diabetes.

Type 2 diabetes (T2DM) subjects failing diet treatment are characterized by hyperinsulinemia and insulin resistance leading to fasting and postprandial hyperglycemia and hyperlipidemia. Energy is essential for allowing the process of protein synthesis to proceed. Additionally, insulin can stimulate protein synthesis in human muscle.

Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases.

Muscle protein synthesis requires energy and amino acids to proceed and can be stimulated by insulin under certain circumstances. We hypothesized that short-term provision of insulin and nutritional energy would stimulate muscle protein synthesis in healthy subjects only if amino acid availability did not decrease. Using stable isotope techniques, we compared the effects on muscle phenylalanine kinetics across the leg of an amino acid-lowering, high-energy (HE, n = 6, 162 +/- 20 kcal/h) hyperglycemic hyperlipidemic hyperinsulinemic clamp with systemic insulin infusion to a low-energy (LE, n = 6, 35 +/- 3 kcal/h, P < 0.