Glucose kinetics and substrate oxidation during exercise in the follicular and luteal phases.

The purpose of this investigation was to determine whether plasma glucose kinetics and substrate oxidation during exercise are dependent on the phase of the menstrual cycle. Once during the follicular (F) and luteal (L) phases, moderately trained subjects [peak O(2) uptake (V(O(2))) = 48.2 +/- 1.1 ml. min(-1). kg(-1); n = 6] cycled for 25 min at approximately 70% of the V(O(2)) at their respective lactate threshold (70%LT), followed immediately by 25 min at 90%LT. Rates of plasma glucose appearance (R(a)) and disappearance (R(d)) were determined with a primed constant infusion of [6,6-(2)H]glucose, and total carbohydrate (CHO) and fat oxidation were determined with indirect calorimetry. At rest and during exercise at 70%LT, there were no differences in glucose R(a) or R(d) between phases. CHO and fat oxidation were not different between phases at 70%LT. At 90%LT, glucose R(a) (28.8 +/- 4.8 vs. 33.7 +/- 4.5 micromol. min(-1). kg(-1); P < 0.05) and R(d) (28.4 +/- 4.8 vs. 34.0 +/- 4.1 micromol. min(-1). kg(-1); P < 0.05) were lower during the L phase. In addition, at 90%LT, CHO oxidation was lower during the L compared with the F phase (82.0 +/- 12.3 vs. 93.8 +/- 9.7 micromol. min(-1) .kg(-1); P < 0.05). Conversely, total fat oxidation was greater during the L phase at 90%LT (7.46 +/- 1.01 vs. 6.05 +/- 0.89 micromol. min(-1). kg(-1); P < 0.05). Plasma lactate concentration was also lower during the L phase at 90%LT concentrations (2.48 +/- 0.41 vs. 3.08 +/- 0.39 mmol/l; P < 0.05). The lower CHO utilization during the L phase was associated with an elevated resting estradiol (P < 0.05). These results indicate that plasma glucose kinetics and CHO oxidation during moderate-intensity exercise are lower during the L compared with the F phase in women. These differences may have been due to differences in circulating estradiol.

Low-fat diet alters intramuscular substrates and reduces lipolysis and fat oxidation during exercise.

We determined whether a low-fat diet reduces intramuscular triglyceride (IMTG) concentration, whole body lipolyis, total fat oxidation, and calculated nonplasma fatty acid (FA) oxidation during exercise. Seven endurance-trained cyclists were studied over a 3-wk period during which time they exercised 2 h/day at 70% of maximum O2 uptake VO(2 max) and consumed approximately 4,400 kcal/day. During the 1st wk, their fat intake provided 32% of energy. During the 2nd and 3rd wk, they were randomly assigned to eat 2 or 22% of energy from fat (2%FAT or 22%FAT). Compared with 22%FAT, 2%FAT lowered IMTG concentration and raised muscle glycogen concentration at rest (P < 0.05). Metabolism was studied during 1 h of exercise at 67% VO(2 max) performed in the fasted state. 2%FAT resulted in a 27% reduction (P < 0.05) in total fat oxidation vs. 22%FAT without altering the stable isotopically determined rates of plasma free fatty acid or glucose disappearance. Therefore, 2%FAT reduced calculated nonplasma FA oxidation by 40% in association with a 19% reduction in whole body lipolysis while increasing calculated minimal muscle glycogen oxidation compared with 22%FAT (all P < 0.05). In summary, an extremely low fat (2% of energy) and high-carbohydrate diet lowers whole body lipolysis, total fat oxidation, and nonplasma FA oxidation during exercise in the fasted state in association with a reduced concentration of intramuscular triglyceride.

Prevention and treatment of non-insulin-dependent diabetes mellitus.

The benefits of exercise training in the prevention and treatment of insulin resistance, impaired glucose homeostasis, and NIDDM are strongly supported by current research. The actual mechanisms involved have not been completely identified but occur at the systemic, tissue, and cellular levels. The adaptations that are responsible for the prophylactic effects of exercise training, however, start to subside rapidly once training ceases and are completely lost within 1 to 2 weeks of detraining [4, 17, 37, 68, 161]. Thus, the benefits of exercise training must be renewed on a regular basis. In addition, many of the systemic and cellular adaptations that are responsible for an improved skeletal muscle insulin action occur in only those muscles involved in the training program [4, 28]. Therefore, exercise training programs that consist of various modes of exercise, and which require the use of a large muscle mass, such as swimming, power walking, and strength training, may be the most advantageous for the prevention and treatment of insulin resistance and associated diseases.

Beta ig-h3, a transforming growth factor-beta-inducible gene, is overexpressed in atherosclerotic and restenotic human vascular lesions.

Transforming growth factor-beta (TGF-beta) plays an important role in vascular lesion formation and possibly the renarrowing process ("restenosis") that occurs after balloon angioplasty. Secreted in a latent form by most cells, TFG-beta requires enzymatic conversion before it is biologically active. TGF-beta-inducible gene h3 (beta ig-h3) is a novel molecule that is induced when cells are treated with TGF-beta1. This study examined the expression of beta ig-h3 in normal and diseased human vascular tissue. To determine the expression pattern of beta ig-h3 in human arteries, immunocytochemistry was performed on tissue sections from (1) normal internal mammary arteries, (2) the proximal left anterior descending coronary artery (with minimal intimal thickening) of 15 patients aged 18 to 40 years, (3) primary and restenotic coronary lesions from 7 patients, and (4) fresh directional atherectomy tissue from 11 patients. A polyclonal antibody consistently immunodetected beta ig-h3 protein in endothelial cells of all vascular tissue. In normal coronary arteries of young individuals, beta ig-h3 protein was absent from the intima and media but was found in the subendothelial smooth muscle cells of some arteries with modest intimal thickening. In diseased arteries beta ig-h3 protein was more abundant in the intima than the media. Restenotic coronary lesions tended to show higher levels of immunodetectable beta ig-h3 protein, especially in areas of dense fibrous connective tissue. Beta ig-h3 protein was immunodetected in the cytoplasm of plaque macrophages as well as smooth muscle and endothelial cells. By using in situ hybridization on fresh directional atherectomy specimens, we found beta ig-h3 mRNA to be overexpressed by plaque macrophages and smooth muscle cells. Nondiseased human internal mammary arteries also expressed beta ig-h3 mRNA in endothelial cells but not in the smooth muscle cells of the normal intima and media. These results document the expression of beta ig-h3 in diseased human arterial tissue and support the hypothesis that active TGF-beta plays a role in atherogenesis and restenosis.