Transcriptomics in tissue glucocorticoid sensitivity.

BACKGROUND: Synthetic glucocorticoids are widely used in the treatment of several inflammatory, autoimmune and lymphoproliferative disorders. However, considerable variation in response to therapeutic doses of glucocorticoids has been documented among individuals. The aim of our study was to identify novel glucocorticoid sensitivity-determining genes using genome-wide expression profiling in healthy subjects. METHODS: One hundred one healthy subjects [mean age ± standard error of the mean (SEM); 26.52 ± 0.50 years] were given 0.25 mg dexamethasone at midnight, and serum cortisol concentrations were determined at 08:00 hours the following morning. Subjects were stratified into the 10% most glucocorticoid-sensitive and 10% most glucocorticoid-resistant according to the serum cortisol concentrations. Genomic DNA, RNA and plasma samples were obtained in the 22 subjects one month later. RESULTS: Transcriptomic analysis showed variability between glucocorticoid-resistant and glucocorticoid-sensitive subjects. One hundred thirty-three genes were upregulated and 49 downregulated in the glucocorticoid-resistant compared to the glucocorticoid-sensitive group. Further analysis revealed differences between 3 glucocorticoid-resistant and 3 glucocorticoid-sensitive subjects. The majority of the 1058 upregulated genes and 1139 downregulated genes were found to participate in telomere maintenance, systemic lupus erythematosus and Alzheimer's disease. Interestingly, Synuclein A, a key molecule in Parkinson's disease, was upregulated in the subgroup of glucocorticoid-sensitive subjects. CONCLUSIONS: We have identified differences in tissue sensitivity to glucocorticoids among healthy subjects at the transcriptomic level. These differences are associated with differential expression of genes related to autoimmune and neurological disorders.

Effect of honey on glucose and insulin concentrations in obese girls.

BACKGROUND: Childhood obesity represents a major health problem of our century. The benefits of natural products, such as honey, in the management of obesity have gained renewed interest. In this study, we investigated the effect of honey on glucose and insulin concentrations in obese prepubertal girls. MATERIALS AND METHODS: Thirty healthy obese girls aged 10.55 (±SEM:0.34) years with a mean body mass index (BMI) above the 97th centile for age (28.58 ± 1.40 kg/m2 , BMI z-score 2.96) underwent a standard oral glucose tolerance test (OGTT) followed by an oral honey tolerance test (OHTT) 2 weeks later. Both solutions contained 75 g of glucose. Subsequently, subjects were randomized to receive either 15 g of honey or 15 g of marmalade daily, while both groups complied with dietetic instructions. Six months later all subjects were re-evaluated with an OGTT and an OHTT. RESULTS: At the end of the study, all subjects demonstrated a significant reduction in BMI (27.57 ± 1.40, z-score: 2.54 vs 28.58 ± 1.40 kg/m2 , z-score: 2.96, P < 0.001), however, there were no significant differences in BMI and all parameters tested between the group that received honey and the control group. The areas under the concentration-time curve for glucose and insulin for the entire population were significantly lower following ingestion of honey than glucose solution (P < 0.001) both at the beginning and at the end of study. CONCLUSIONS: These findings indicate that honey does not have an effect on stimulated plasma glucose and serum insulin concentrations compared with the standard glucose solution in obese prepubertal girls.