Repeated post-exercise administration with a mixture of leucine and glucose alters the plasma amino acid profile in Standardbred trotters

<p>Abstract</p> <p>Background</p> <p>The branched chain amino acid leucine is a potent stimulator of insulin secretion. Used in combination with glucose it can increase the insulin response and the post exercise re-synthesis of glycogen in man. Decreased plasma amino acid concentrations have been reported after intravenous or per oral administration of leucine in man as well as after a single per oral dose in horses. In man, a negative correlation between the insulin response and the concentrations of isoleucine, valine and methionine have been shown but results from horses are lacking. This study aims to determine the effect of repeated per oral administration with a mixture of glucose and leucine on the free amino acid profile and the insulin response in horses after glycogen-depleting exercise.</p> <p>Methods</p> <p>In a crossover design, after a glycogen depleting exercise, twelve Standardbred trotters received either repeated oral boluses of glucose, 1 g/kg body weight (BW) at 0, 2 and 4 h with addition of leucine 0.1 g/kg BW at 0 and 4 h (GLU+LEU), or repeated boluses of water at 0, 2 and 4 h (CON). Blood samples for analysis of glucose, insulin and amino acid concentrations were collected prior to exercise and over a 6 h post-exercise period. A mixed model approach was used for the statistical analyses.</p> <p>Results</p> <p>Plasma leucine, isoleucine, valine, tyrosine and phenylalanine concentrations increased after exercise. Post-exercise serum glucose and plasma insulin response were significantly higher in the GLU+LEU treatment compared to the CON treatment. Plasma leucine concentrations increased after supplementation. During the post-exercise period isoleucine, valine and methionine concentrations decreased in both treatments but were significantly lower in the GLU+LEU treatment. There was no correlation between the insulin response and the response in plasma leucine, isoleucine, valine and methionine.</p> <p>Conclusions</p> <p>Repeated post-exercise administration with a mixture of leucine and glucose caused a marked insulin response and altered the plasma amino acid profile in horses in a similar manner as described in man. However, the decreases seen in plasma amino acids in horses seem to be related more to an effect of leucine and not to the insulin response as seen in man.</p

The Effect of High Glucocorticoid Administration and Food Restriction on Rodent Skeletal Muscle Mitochondrial Function and Protein Metabolism

Glucocorticoids levels are high in catabolic conditions but it is unclear how much of the catabolic effects are due to negative energy balance versus glucocorticoids and whether there are distinct effects on metabolism and functions of specific muscle proteins.We determined whether 14 days of high dose methylprednisolone (MPred, 4 mg/kg/d) Vs food restriction (FR, food intake matched to MPred) in rats had different effects on muscle mitochondrial function and protein fractional synthesis rates (FSR). Lower weight loss (15%) occurred in FR than in MPred (30%) rats, while a 15% increase occurred saline-treated Controls. The per cent muscle loss was significantly greater for MPred than FR. Mitochondrial protein FSR in MPred rats was lower in soleus (51 and 43%, respectively) and plantaris (25 and 55%) than in FR, while similar decline in protein FSR of the mixed, sarcoplasmic, and myosin heavy chain occurred. Mitochondrial enzymatic activity and ATP production were unchanged in soleus while in plantaris cytochrome c oxidase activity was lower in FR than Control, and ATP production rate with pyruvate + malate in MPred plantaris was 28% lower in MPred. Branched-chain amino acid catabolic enzyme activities were higher in both FR and MPred rats indicating enhanced amino acid oxidation capacity.MPred and FR had little impact on mitochondrial function but reduction in muscle protein synthesis occurred in MPred that could be explained on the basis of reduced food intake. A greater decline in proteolysis may explain lesser muscle loss in FR than in MPred rats

Rosiglitazone-associated fractures in type 2 diabetes

OBJECTIVE - The purpose of this study was to examine possible factors associated with the increased risk of fractures observed with rosiglitazone in A Diabetes Outcome Progression Trial (ADOPT). RESEARCH DESIGN AND METHODS - Data from the 1,840 women and 2,511 men randomly assigned in ADOPT to rosiglitazone, metformin, or glyburide for a median of 4.0 years were examined with respect to time to first fracture, rates of occurrence, and sites of fractures. RESULTS - In men, fracture rates did not differ between treatment groups. In women, at least one fracture was reported with rosiglitazone in 60 patients (9.3% of patients, 2.74 per 100 patient-years), metformin in 30 patients (5.1%, 1.54 per 100 patient-years), and glyburide in 21 patients (3.5%, 1.29 per 100 patient-years). The cumulative incidence (95% CI) of fractures in women at 5 years was 15.1% (11.2-19.1) with rosiglitazone, 7.3% (4.4-10.1) with metformin, and 7.7% (3.7-11.7) with glyburide, representing hazard ratios (95% CI) of 1.81 (1.17-2.80) and 2.13 (1.30-3.51) for rosiglitazone compared with metformin and glyburide, respectively. The increase in fractures with rosiglitazone occurred in pre- and postmenopausal women, and fractures were seen predominantly in the lower and upper limbs. No particular risk factor underlying the increased fractures in female patients who received rosiglitazone therapy was identified. CONCLUSIONS-Further investigation into the risk factors and underlying pathophysi-ology for the increased fracture rate in women taking rosiglitazone is required to relate them to preclinical data and better understand the clinical implications of and possible interventions for these findings. © 2008 by the American Diabetes Association

Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT).

OBJECTIVE: The purpose of this study was to examine possible factors associated with the increased risk of fractures observed with rosiglitazone in A Diabetes Outcome Progression Trial (ADOPT). RESEARCH DESIGN AND METHODS: Data from the 1,840 women and 2,511 men randomly assigned in ADOPT to rosiglitazone, metformin, or glyburide for a median of 4.0 years were examined with respect to time to first fracture, rates of occurrence, and sites of fractures. RESULTS: In men, fracture rates did not differ between treatment groups. In women, at least one fracture was reported with rosiglitazone in 60 patients (9.3% of patients, 2.74 per 100 patient-years), metformin in 30 patients (5.1%, 1.54 per 100 patient-years), and glyburide in 21 patients (3.5%, 1.29 per 100 patient-years). The cumulative incidence (95% CI) of fractures in women at 5 years was 15.1% (11.2-19.1) with rosiglitazone, 7.3% (4.4-10.1) with metformin, and 7.7% (3.7-11.7) with glyburide, representing hazard ratios (95% CI) of 1.81 (1.17-2.80) and 2.13 (1.30-3.51) for rosiglitazone compared with metformin and glyburide, respectively. The increase in fractures with rosiglitazone occurred in pre- and postmenopausal women, and fractures were seen predominantly in the lower and upper limbs. No particular risk factor underlying the increased fractures in female patients who received rosiglitazone therapy was identified. CONCLUSIONS: Further investigation into the risk factors and underlying pathophysiology for the increased fracture rate in women taking rosiglitazone is required to relate them to preclinical data and better understand the clinical implications of and possible interventions for these findings