Altered regulation of energy homeostasis in older rats in response to thyroid hormone administration.

Hyperthyroidism causes increased energy intake and expenditure, although anorexia and higher weight loss have been reported in elderly individuals with hyperthyroidism. To determine the effect of age on energy homeostasis in response to experimental hyperthyroidism, we administered 200 μg tri-iodothyronine (T3) in 7- and 27-mo-old rats for 14 d. T3 increased energy expenditure (EE) in both the young and the old rats, although the old rats lost more weight (147 g) than the young rats (58 g) because of the discordant effect of T3 on food intake, with a 40% increase in the young rats, but a 40% decrease in the old ones.

Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement.

Systemic insulin administration causes hypoaminoacidemia by inhibiting protein degradation, which may in turn inhibit muscle protein synthesis (PS). Insulin enhances muscle mitochondrial PS and ATP production when hypoaminoacidemia is prevented by exogenous amino acid (AA) replacement. We determined whether insulin would stimulate mitochondrial PS and ATP production in the absence of AA replacement.

Asian Indians have enhanced skeletal muscle mitochondrial capacity to produce ATP in association with severe insulin resistance.

Objective: Type 2 diabetes has become a global epidemic, and Asian Indians have a higher susceptibility to diabetes than Europeans. We investigated whether Indians had any metabolic differences compared with Northern European Americans that may render them more susceptible to diabetes.

Research Design And Methods: We studied 13 diabetic Indians, 13 nondiabetic Indians, and 13 nondiabetic Northern European Americans who were matched for age, BMI, and sex.

Enhancement of muscle mitochondrial function by growth hormone.

Context: Although GH promotes growth and protein anabolism, which are ATP-dependent processes, the GH effect on mitochondrial regulation remains to be determined.

Objective: Our objective was to determine the acute effect of GH on mitochondrial oxidative capacity in skeletal muscle of healthy subjects.

Design And Setting: The study was a randomized crossover design at an academic medical center.

Effect of insulin deprivation on muscle mitochondrial ATP production and gene transcript levels in type 1 diabetic subjects.

Objective: Muscle mitochondrial dysfunction occurs in many insulin-resistant states, such as type 2 diabetes, prompting a hypothesis that mitochondrial dysfunction may cause insulin resistance. We determined the impact of insulin deficiency on muscle mitochondrial ATP production by temporarily depriving type 1 diabetic patients of insulin treatment.

Research Design And Methods: We withdrew insulin for 8.

Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia.

We investigated whether previously reported muscle mitochondrial dysfunction and altered gene transcript levels in type 2 diabetes might be secondary to abnormal blood glucose and insulin levels rather than an intrinsic defect of type 2 diabetes. A total of 13 type 2 diabetic and 17 nondiabetic subjects were studied on two separate occasions while maintaining similar insulin and glucose levels in both groups by 7-h infusions of somatostatin, low- or high-dose insulin (0.25 and 1.

Changes in skeletal muscle protein metabolism and myosin heavy chain isoform messenger ribonucleic acid abundance after treatment of hyperthyroidism.

Background: Hyperthyroidism causes a hypermetabolic state and skeletal muscle dysfunction, but the underlying mechanism remains incompletely defined.

Objective: The objective of the study was to determine whether treatment of hyperthyroidism causes changes in amino acid fluxes, synthesis rates of muscle proteins, and expression of muscle myosin heavy chain (MHC) that may impact skeletal muscle function and metabolic rate.

Methods: Eight hyperthyroid patients were studied (TSH 0.

Decline in skeletal muscle mitochondrial function with aging in humans.

Cumulative mtDNA damage occurs in aging animals, and mtDNA mutations are reported to accelerate aging in mice. We determined whether aging results in increased DNA oxidative damage and reduced mtDNA abundance and mitochondrial function in skeletal muscle of human subjects. Studies performed in 146 healthy men and women aged 18-89 yr demonstrated that mtDNA and mRNA abundance and mitochondrial ATP production all declined with advancing age.

Changes in myosin heavy chain mRNA and protein expression in human skeletal muscle with age and endurance exercise training.

Aging is associated with reduced muscle strength and atrophy of type II muscle fibers. Muscle fiber type and contractile function are primarily determined by myosin heavy chain (MHC) isoforms. There are few data available on the effects of aging on MHC isoform expression in humans.

Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity.

Insulin resistance increases and muscle oxidative capacity decreases during aging, but lifestyle changes-especially physical activity-may reverse these trends. Here we report the effect of a 16-week aerobic exercise program (n = 65) or control activity (n = 37) performed by men and women aged 21-87 years on insulin sensitivity and muscle mitochondria. Insulin sensitivity, measured by intravenous glucose tolerance test, decreased with age (r = -0.

Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment.

Type 2 diabetes is characterized by muscle insulin resistance. Nondiabetic first-degree relatives of type 2 diabetic patients have also been reported to have insulin resistance. A polygenic basis for pathogenesis of type 2 diabetes has been proposed.