Syndrom polycystických ovarií (PCOS) se považuje za jednu z nejčastěji se vyskytujících endokrinopatií u žen ve fertilním věku. Ženy trpící PCOS jsou ve 30–80 % současně obézní a obezita je často doprovázena hyperinzulinemií a inzulinovou rezistencí, a to i nezávisle na BMI. Většina publikovaných prací prokazuje u žen s PCOS zvýšený výskyt diabetes mellitus 2. typu. U žen s PCOS je 2,89krát vyšší riziko vzniku gestačního diabetu nežli u kontrolních pacientek. Doporučuje se proto provádět screening orálním glukózovým tolerančním testem. Prvním opatřením v péči o obézní pacientky s PCOS je úprava životního stylu, byť chybí pro toto opatření opora v dostatečném množství kontrolovaných studií na toto téma. Pokud nedojde k úpravě porušené glukózové tolerance, je indikován metformin, u nějž ovšem také chybí dostatek údajů o podávání gravidním s cílem prevence rozvoje GDM. PCOS se ovšem vyskytuje až u 30 % žen s diabetes mellitus 1. typu a bývá spojován s terapií inzulinem. Dosavadní pilotní studie prokazují, že se v terapii příznivě uplatňuje metformin, a u žen, které nechtějí otěhotnět, kombinovaná hormonální kontraceptiva s neandrogenními gestageny. Klíčová slova: diabetes mellitus – gestageny – kombinovaná hormonální kontraceptiva – metformin – orální glukózový toleranční test – porušená glukózová tolerance – syndrom polycystických ovarií, Polycystic ovary syndrome (PCOS) is considered one of the most common endocrinopathies in women of childbearing age. 30 – 80 % of women suffering from PCOS are obese and obesity is often accompanied by hyperinsulinemia and insulin resistance, even independently of body mass index. Most of the published works have demonstrated an increased incidence of type 2 diabetes in women with PCOS. There is 2,89 times higher risk of developing gestational diabetes in women with PCOS comparing to control group. Therefore, it is recommended to perform oral glucose tolerance test. It is highly recommended to begin with lifestyle changes as the first step in treating obese woman with PCOS although there is lack of evidence from controlled trials. If impaired glucose tolerance does not improve, metformin is indicated, but there is lack of data on the use in pregnant women as a prevention of GDM development. PCOS occurs in up to 30% of women with type 1 diabetes and is associated with insulin therapy. The existing pilot studies have demonstrated that metformin is useful in therapy. The combined hormonal contraceptives with non-androgenic gestagens are applied in women who do not want to be pregnant. Key words: combined hormonal contraceptives – diabetes mellitus – gestagens – impaired glucose tolerance – metformin – oral glucose tolerance test – polycystic ovary syndrome, and Jana Vrbíková
Bradykinin can enhance skeletal muscle glucose uptake (GU), and exercise increases both br adykinin production and muscle insulin sensitivity, but bradykinin’s relationship with post-exercise insulin action is uncertain. Our primary aim was to determine if the B2 receptor of bradykinin (B2R) is essential for the post- exercise increase in GU by insulin-stimulated mouse soleus muscles. Wildtype (WT) and B2 R knockout (B2RKO) mice were sedentary or performed 60 minutes of treadmill exercise. Isolated soleus muscles were incubated with [ 3 H]-2-deoxyglucose ±insulin (60 or 100 μ U/ml). GU tended to be greater for WT vs. B2RKO soleus with 60 μ U/ml insulin (P=0.166) and was significantly greater for muscles with 100 μ U/ml insulin (P<0.05). Both genotypes had significant exercise-induced reductions (P<0.05) in glycemia and insulinemia, and the decrements for glucose (~14 %) and insulin (~55 %) were similar between genotypes. GU tended to be greater for exercised vs. sedentary soleus with 60 μ U/ml insulin (P=0.063) and wa s significantly greater for muscles with 100 μ U/ml insulin (P<0.05). There were no significant interactions between genotype and exercise for blood glucose, plasma insulin or GU. These results indicate that the B2R is not essential for the exerci se-induced decrements in blood glucose or plasma insulin or for the post-exercise increase in GU by insulin-stimulated mouse soleus muscle., G. G. Schweitzer ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin -like -growth- factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide -3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percenta ge of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA -IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF -binding protein-3 (IGFBP-3) expression that both positively correlated wit h serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA -IR while IGFBP -3 expression in SCAT was an independ ent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly., V. Touskova, J. Klouckova, V. Durovcova, Z. Lacinova, P. Kavalkova, P. Trachta, M. Kosak, M. Mraz, D. Haluzikova, V. Hana, J. Marek, M. Krsek, M. Haluzik., and Obsahuje bibliografii
The skin matrix metalloproteinase 3, tissue inhibitors of matrix metalloproteinase 2 and collagen III content changes in type 1 diabetes and insulin resistance treated with insulin a nd metformin were studied. Healthy adult male Wistar rats were obtained from experimental animal house, Department of Experimental Pharmacology, Medical University in Bialystok. The rats were divided randomly into five groups of 8 rats each. Control rats were injected intraperitoneally by NaCl. Type IDDM was induced by a single injection of Streptozocin. Insulin resistance was induced by a high -fat diet. The chosen groups of rats were also treated with insulin or metformin. ELISA K its (USCN Life Science, China) were used to measure content of matrix metallo - proteinase 3 (ELISA Kit for Matrix Metalloproteinase 3 - MMP3), tissue inhibitor of matrix metalloproteinase 2 (ELISA Kit for Tissue Inhibitors of Metalloproteinase 2 - TIMP2) and content of collagen type 3 (ELISA Kit for Collagen Type III - COL3). The results were reported as a median. The statistical significance was defined as p<0.05. Type 1 diabetes and insulin resistance have significantly reduced the quality of the skin, shown by the increase in cont ent of matrix metalloproteinase 3 and the decrease in content of tissue inhibitors of matrix metalloproteinase 2. Type 1 diabetes and insulin resistance have reduced the quality of the skin expressed by type III collagen content decrease but for future studies it is recommend to determine rat interstitial collagenase, MMP -13, as well. Insulin and metformin treatment improved the quality of the diabetic skin, demonstrated by the type III collagen content increase., M. Knaś, K. Wołosik, A. Zalewska, A. Mikucka-Niczyporuk, I. Kasacka, M. Niczyporuk., and Obsahuje bibliografii
Spontaneously hypertensive rats (SHR/NIH strain) harbor a deletion variant in the Cd36 fatty acid transporter and display defective fatty acid metabolism, insulin resistance and hypertension. Transgenic rescue of Cd36 in SHR ameliorates insulin resistance and improves dyslipidemia. However, the role of Cd36 in blood pressure regulation remains controversial due to inconsistent blood pressure effects that were observed with transgenic expression of Cd36 on the SHR background. In the current studies, we developed two new SHR transgenic lines, which express wild type Cd36 under the control of the universal Ef-1 promoter, and examined the effects of transgenic expression of wild type Cd36 on selected metabolic and cardiovascular phenotypes. Transgenic expression of Cd36 in the new lines was associated with significantly decreased serum fatty acids, amelioration of insulin resistance and glucose intolerance but failed to induce any consistent changes in blood pressure as measured by radiotelemetry. The current findings confirm the genetic association of defective Cd36 with disordered insulin action and fatty acid metabolism in the SHR/NIH strain and suggest that Cd36 is linked to other gene(s) on rat chromosome 4 that regulate blood pressure., M. Pravenec, V. Landa, V. Zídek, A. Musilová, L. Kazdová, N. Qi, J. Wang, E. St.Lezin, T. W. Kurtz., and Obsahuje bibliografii
Cíl: Gen pro adiponektin bývá označován jako kandidátní gen inzulinové rezistence (IR). V naší práci byl sledován možný vztah mezi jednonukleotidovým polymorfi smem (SNP) +276 G > T a markery inzulinové rezistence včetně lipidového a lipoproteinového profi lu u 355 dyslipidemických pacientů lipidové ambulance III. interní kliniky Fakultní nemocnice Olomouc a jejich prvostupňových příbuzných. Metody: SNP genu pro adiponektin byl detekován metodou polymerázové řetězové reakce v reálném čase s hybridizačními fl uorescenčními sondami. Rozdíly mezi genotypy ve spojitých proměnných byly analyzovány metodou ANOVA (upraveno na věk, pohlaví a obvod pasu). Výsledky: Nosiči genotypu GG měli významně vyšší hladiny celkového cholesterolu (GG: 6,54 ± 1,74 mmol/l, GT: 6,18 ± 1,45 mmol/l, TT: 6,25 ± 1,64 mmol/l, p < 0,05) a LDL cholesterolu (GG: 4,12 ± 1,49 mmol/l, GT: 3,78 ± 1,31 mmol/l, TT: 3,70 ± 1,34 mmol/l, p < 0,05) než jedinci s alelou T. Přítomnost alely T na pozici 276 byla u heterozygotů naopak spojena s vyšší koncentrací inhibitoru aktivátoru plasminogenu 1 (PAI-1) (GG: 71,50 ± 41,0 μg/l, GT: 81,0 ± 38,7 μg/l, TT: 70,14 ± 44,4 μg/l, p < 0,05). Závěr: Ve studii byla zjištěna slabá asociace heterozygotů-nosičů T alely polymorfi smu +276 G > T genu pro adiponektin a jedním markerem inzulinové rezistence, avšak nebyl nalezen vztah k sérovému adiponektinu, inzulinu, body mass indexu a dyslipidemickým fenotypům., Aim: The adiponectin gene has been proposed as a potential candidate gene for IR. We analysed possible relationship between +276 G > T SNP and IR markers together with lipid and lipoprotein profi les in 355 Czech dyslipidemic patients of Lipid Center, University Hospital Olomouc, and their fi rst degree relatives. Methods: The +276 G > T SNP of adiponectin gene was detected by real time PCR method with hybridization fl uorescence probes in LightCycler. Between-genotype differences in continuous variables were analyzed by ANOVA after adjustment for age, sex and waist circumference. Results: Subjects with GG genotype were associated with higher total cholesterol (GG: 6.54 ± 1.74 mmol/l, GT: 6.18 ± 1.45 mmol/l, TT: 6.25 ± 1.64 mmol/l, p < 0.05) and LDL cholesterol (GG: 4.12 ± 1.49 mmol/l, GT: 3.78 ± 1.31 mmol/l, TT: 3.70 ± 1.34 mmol/l, p < 0.05) in comparison with T allele carriers. On the contrary, the presence of T allele in position 276 in heterozygotes was associated with higher levels of plasma inhibitor of activator of plasminogen 1 (PAI-1) (GG: 71.50 ± 41.0 μg/l, GT: 81.0 ± 38.7 μg/l, TT: 70.14 ± 44.4 μg/l, p < 0.05). Conclusion: In this study, the poor association between carriers- heterozygotes of T alelle of +276 G > T polymorphism of gene for adiponectin and one marker of insulin resistance was found. However, no relationship was detected with plasma adiponectin, insulin, body mass index and dyslipidemic phenotypes., Novotný Dalibor, Vaverková H., Karásek D., Halenka M., Lukeš J., Slavík L., Bartková M., Schneiderka P., and Lit.: 11
Zásah porušené regulace metabolizmu glukózy do metabolizmu kostní tkáně je mnohostranný a velmi komplikovaný. Ve většině případů nacházíme u diabetiků zvýšené riziko zlomenin. Důvody, které k tomuto stavu vedou, jsou mnohočetné. U diabetiků nebývá hlavní příčinou pokles kostní minerální hustoty, spíše jde o snížení kvality kostní tkáně a změnu její struktury. Významnou roli hraje nepochybně inzulin a inzulinová rezistence, uplatňuje se ale i zvýšená glykace proteinů, včetně zvýšené glykace kolagenu v kostech, změna produkce a hladiny sklerostinu, zásah do diferenciace pluripotentních kmenových buněk a zvrat jejich diferenciace směrem k adipocytům a mnohé další faktory. Nemalý podíl na zvýšeném riziku fraktur mohou mít i některá antidiabetika, především perorální. Vzhledem ke stoupající incidenci obou chorob, diabetu i osteoporózy, bude nezbytné podrobněji zkoumat i jejich vzájemné vazby a ovlivnění. Klíčová slova: antidiabetika – diabetes mellitus – inzulinová rezistence – metabolizmus kostí – osteoporóza, The effect of impaired regulation of the glucose metabolism on the bone tissue metabolism is many-sided and very complicated. In most cases we observe an increased risk of fracture in people with diabetes. The reasons causing this condition are varied. Its main cause in diabetic patients is typically not the decrease in bone mineral density, it is rather deterioration of bone tissue and its structure. An important role of insulin and insulin resistance is beyond dispute, with numerous other factors at work, such as increased glycation of proteins, including increased glycation of collagen in bones, change in sclerostin production and levels, intervention in the pluripotent stem cells differentiation and reversal of their differentiation toward adipocytes and many more. Some antidiabetics, mainly oral, may also significantly contribute to the increased risk of fracture. Given the increasing incidence of both diseases, diabetes and osteoporosis, it will be also necessary to examine in greater detail their mutual relations and effects. <p align="">Key words: antidiabetics – bone metabolism – diabetes mellitus – insulin resistance – osteoporosis, and Vladimír Palička, Jana Lesná, Ladislava Pavlíková