[Effects of catalase gene (RS769217) polymorphism on energy homeostasis and bone status are gender specific]. / Nemhez kötött a katalázgén-polimorfizmus (RS769217) hatása az energia-háztartásra és a csontok állapotára.

The pathogenic role of oxidative stress has already been proven both in energy homeostasis and bone metabolism. The effects of +22348C>T (RS769217) polymorphism of catalase (EC 1.11.1.6, hydrogenperoxid-hydrogenperoxid oxidoreduktase) gene were investigated on glucose disposal and bone mineral density in groups of healthy (n = 24) and glucose intolerant (n = 27) females and healthy (n = 64) and glucose intolerant (n = 26) males. Glucose intolerant groups included IFG, IGT and non-treated type 2 diabetic patients. There were no differences in allele frequencies between the genders and groups in this transdanubian Hungarian population. The effects of CAT gene polymorphisms on glucose metabolism and bone status were gender specific. Females with mutant CAT (CT+TT) gene had better HOMA-IR (CC: 2.95+/-1.8 versus CT+TT: 2.06+/-0.9, p<0.05), but bone density did not differ between the CC and CT+TT haplotypes. The homozygote TT females had significantly better whole body glucose disposal. (M-1 mg/kg/min: CC: 9,43+/-4,4 versus TT: 13,23+/-1,6mg/kg body weight/min, p<0.05). The appearance of T allel among males caused lower femur density (CC: 1,11+/-0,17 versus CT+TT: 1,03+/-0,16, p<0.05 g/cm 2 ) and better HOMA-IR (CC: 2.42+/-2.3 versus CT+TT: 1.50+/-0.2, p<0.05), with no change in whole body glucose disposal. Osteocalcin - which has been proven to be the connection between energy homeostasis and bone metabolism - had identical serum levels in both haplotypes, but the significant correlation between muscle tissue glucose utilization and osteocalcin levels (r = +0.4424, p<0.05, n = 23) disappeared in the presence of T allele. Multiple correlation showed significant connection between leptin/adiponectin and femur BMD in CC female group, and between leptin/adiponectin and lumbar BMD in CC male group. The correlations disappeared with the appearance of T allele. Our results differ from the data obtained in Korean postmenopausal women and stress the need of population/ethnic specific replication of genetic data.

[Occurrence of GRB10 (+11275G > A) polymorphism in Hungarian population and its relationship to glucose metabolism]. / A GRB10 gén (+11275G > A) polimorfizmusának hazai elôfordulása és kapcsolata a cukoranyagcserével.

In our backstage experiment with differential display method among the differentially expressed genes we found the gene of GRB10 (Growth factor Receptor-Bound protein 10). The GRB10 protein binds to insulin and insulin-like growth factor receptors and acts as a negative regulatory protein. Besides, GRB10 gene polymorphisms are connected to the development of type 2 diabetes mellitus. In this experiment we investigated the allele frequency of RS 2237457, +11275G > A polymorphism in Hungarian healthy and type 2 diabetic populations (healthy: n = 77, diabetics: n = 85). We also searched for the connections between the genotype and glucose homeostasis measured by hyperinsulinemic - normoglycemic clamps in healthy volunteers (n = 88), glucose intolerant (IFG n = 15; IGT n = 29) and non-treated type 2 diabetic patients (n = 9). We did not find significant differences in allele frequencies between the Hungarian healthy and diabetic populations (healthy: g vs. a: 62% vs. 38%; 2DM g vs. a: 70% vs. 30%). In case of females, glucose utilization did not depend on GRB10 gene polymorphisms. Insulin production after oral glucose load was increased among males with gg alleles, and not after iv. glucose administration. The glucose disposal in muscle tissue was lower and the metabolic clearance rate was also lower calculated either for total body or muscle tissue in this group. In both genders gg alleles were associated with a disadvantageous lipid profile of decreased levels of large, buoyant LDL molecules and HDL levels in females. Metabolic changes related to the polymorphism of GRB10 gene support a gender specific role of this gene in insulin sensitivity and insulin signal transduction. It may be hypothesized on the basis of the differences in insulin release after oral and iv. glucose loads that GRB10 is involved in incretin signaling pathway.

[The role of osteocalcin in the connection of bone and glucose metabolism in humans]. / Az osteocalcin helye a humán cukor- és csontanyagcsere kapcsolatában.

UNLABELLED: The lack of osteoblast derived osteocalcin in mice causes reduced pancreatic beta-cell proliferation, decreased expression of insulin gene and adiponectin gene in adipocytes as well. METHODS: The relationship between insulin sensitivity, osteocalcin and bone state in 45 healthy (20 females, 25 males) and 92 glucose intolerant (51 females, 41 males) subjects was examined. Body composition, bone density, markers of bone resorption and formation as well as glucose uptake (M value for insulin sensitivity) measured by hyperinsulinemic normoglycemic clamp were determined separately in males and females. RESULTS: Osteocalcin levels were similar in the two genders, however, glucose intolerant men had lower osteocalcin levels than healthy men (24.5+/-11 vs. 18.1+/-9 ng/ml, p < 0.05). In the healthy group, we found positive correlation between osteocalcin and muscle M values (females: r = +0.319, p < 0.05, males: r = 0.481, p < 0.01), although this relationship disappeared in the glucose intolerant groups. Osteocalcin did not show correlation with adiponectin level in any of the genders. Based on a multivariate regression analysis, in all females significant independent predictors of osteocalcin level were fasting blood glucose, whole and lean body mass glucose uptake, metabolic clearance rate, estradiol and LDL-cholesterol levels (determined 92% of its value), while in all men these were serum calcium, OGTT glucose area under the curve, free fatty acid levels, insulogenic index, HOMA-R and waist/hip ratio (determined 95% of its value). The BMU index characterizing bone resorption/formation correlated significantly with the M values only in women. CONCLUSION: This study confirmed the relationship between insulin sensitivity and osteocalcin in healthy human population, although basic difference was found between the two genders which was not related to osteocalcin.

[Effect of progressive insulin resistance on the correlation of glucose metabolism and bone status]. / A progrediáló inzulinrezisztencia hatása a glükózanyagcsere csontállapot kapcsolatokra.

A paradox is hidden in the increasing number of patients with insulin resistance, Type 2 diabetes and osteoporosis, as the world wide diabetes epidemic is driven by the same obesity which protects the bones in the obese females. Our aim was to investigate the connection between the early glucose intolerance, insulin resistance and bone density and metabolism. After metabolic status of matched 20 healthy and 51 glucose intolerant women (age: 49 +/- 9 y.) was determined, hyperinsulinemic-euglycemic clamps were done, while adipo- and cytokine levels were measured. Bone mineral density over lumbar spine and the femur neck were measured by DEXA. No differences in bone density were observed between groups at any sites measured. Tight correlations were found between total body glucose utilization and bone density in healthy group (lumbar spine r = -0.4921, p < 0.05, femur neck: r = -0.4972, p < 0.05), while with deterioration of glucose metabolism this correlation disappeared (lumbar spine: r = -0.022, ns; femur neck: r = -0.3136, ns). The adiponectin was the only adipokine which correlated with lumbar spine density in both groups ( r = -0.5081, p < 0.05; -0.2804, p < 0.05), but not with femur density, where this connection disappeared with glucose intolerance ( r = -0.6742, p < 0.01; -0.1723, ns). Relations of bone metabolic markers indicated that bone resorption decreases with worsening of insulin resistance. In conclusion inverse correlations were found between bone density and glucose metabolism, or insulin sensitivity in healthy women in perimenopause, but this connection disappeared with the deterioration of glucose metabolism and progression of insulin resistance measured by the "gold standard" insulin-glucose clamps. Decreasing insulin sensitivity of bones and escape from "metabolic control" may result in frequently observed hyperdensity in Type 2 diabetics.