Carbohydrate metabolism during intense exercise when hyperglycemic

The effects of hyperglycemia on muscle glycogen use and carbohydrate metabolism were evaluated in eight well-trained cyclists (average maximal O2 consumption 4.5 +/- 0.1 l/min) during 2 h of exercise at 73 +/- 2% of maximal O2 consumption. During the control trial (CT), plasma glucose concentration averaged 4.2 +/- 0.2 mM and plasma insulin remained between 6 and 9 microU/ml. During the hyperglycemic trial (HT), 20 g of glucose were infused intravenously after 8 min of exercise, after which a variable-rate infusion of 18% glucose was used to maintain plasma glucose at 10.8 +/- 0.4 mM throughout exercise. Plasma insulin remained low during the 1st h of HT, yet it increased significantly (to 16-24 microU/ml; P less than 0.05) during the 2nd h. The amount of muscle glycogen utilized in the vastus lateralis during exercise was similar during HT and CT (75 +/- 8 and 76 +/- 7 mmol/kg, respectively). As exercise duration increased, carbohydrate oxidation declined during CT but increased during HT. Consequently, after 2 h of exercise, carbohydrate oxidation was 40% higher during HT than during CT (P less than 0.01). The rate of glucose infusion required to maintain hyperglycemia (10 mM) remained very stable at 1.6 +/- 0.1 g/min during the 1st h. However, during the 2nd h of exercise, the rate of glucose infusion increased (P less than 0.01) to 2.6 +/- 0.1 g/min (37 mg.kg body wt-1.min-1) during the final 20 min of exercise. We conclude that hyperglycemia (i.e., 10 mM) in humans does not alter muscle glycogen use during 2 h of intense cycling.(ABSTRACT TRUNCATED AT 250 WORDS)     

v-mos oncoproteins affect the nuclear retention and reutilization of glucocorticoid receptors

Expression of the p85gag-mos oncoprotein in temperature sensitive transformed 6m2 cells results in desensitization of glucocorticoid induction of metallothionein-1 mRNA. Indirect immunofluorescence analyses demonstrate that hormone insensitivity in v-mos transformed cells is associated with inefficient nuclear retention of glucocorticoid receptor (GR) protein. Desensitized receptors that accumulate in the cytoplasm of transformed 6m2 cells do not regain the capacity for hormone-dependent nuclear translocation after turnover of the thermo-labile p85gag-mos oncoprotein. Although ligand induced down-regulation of immunoreactive GR protein occurs in transformed 6m2 cells, desensitized receptors appear to retain some capacity to bind hormone in vivo. Thus alterations in the intracellular partitioning of GR protein in v-mos-transformed cells result in the generation of a novel desensitized receptor that is apparently trapped in the cytoplasm and incapable of being reutilized.     

Oxalyl thiolester concentrations decreased in lectin and phorbol ester-stimulated lymphocytes

Oxalyl thiolesters (OTEs) are a newly discovered class of mammalian metabolites that are believed to function in controlling animal metabolism and possibly serve as intracellular mediators for some hormones. Previous correlations had suggested that the concentrations of OTEs might be decreased when cells are stimulated to proliferate, and in our research that was found to be the case. Thus, when bovine lymph node lymphocytes are stimulated either with concanavalin A (Con A) or with a combination of phytohemagglutinin (PHA) and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), the concentration of OTEs in the lymphocytes decreases within 3 h by a factor of approximately two. With either PHA or TPA alone, the decrease in OTE concentration is considerably smaller. With Con A as stimulant, the OTE levels decrease within 1 h and remain low for at least 24 h. It was also noted that the concentration of OTEs in unstimulated isolated lymphocytes is significantly lower in lymphocytes obtained from 2-year-old animals than in lymphocytes obtained from older animals. The results of the current investigation, when considered in conjunction with other recent results, suggest that OTEs may be natural cell proliferation inhibitors.