impaired glucose utilization
Dotaz
Zobrazit nápovědu
OBJECTIVE: Telmisartan improves glucose and lipid metabolism in rodents. This study evaluated the effect of telmisartan on insulin sensitivity, substrate utilization, selected plasma adipokines and their expressions in subcutaneous adipose tissue (SAT) in metabolic syndrome. DESIGN AND METHODS: Twelve patients with impaired fasting glucose completed the double-blind, randomized, crossover trial. Patients received telmisartan (160 mg/day) or placebo for 3 weeks and vice versa with a 2-week washout period. At the end of each period, a hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry was performed. During HEC (0, 30, and 120 min), plasma levels of adipokines were measured and a needle biopsy (0 and 30 min) of SAT was performed. RESULTS: Fasting plasma glucose was lower after telmisartan compared with placebo (P<0.05). There were no differences in insulin sensitivity and substrate utilization. We found no differences in basal plasma adiponectin, resistin and tumour necrosis factor α (TNFα), but an increase was found in basal leptin, after telmisartan treatment. Insulin-stimulated plasma adiponectin (P<0.05), leptin and resistin (P<0.001) were increased, whereas TNFα was decreased (P<0.05) after telmisartan treatment. Expression of resistin, but not adiponectin, TNFα and leptin was increased after telmisartan treatment. CONCLUSIONS: Despite the decrease in fasting plasma glucose, telmisartan does not improve insulin sensitivity and substrate utilization. Telmisartan increases plasma leptin as well as insulin-stimulated plasma adiponectin, leptin and resistin, and decreases plasma TNFα during HEC. Changes in plasma adipokines cannot be explained by their expressions in SAT. The changes in plasma adipokines might be involved in the metabolic effects of telmisartan in metabolic syndrome.
- MeSH
- adipokiny krev MeSH
- benzimidazoly terapeutické užití MeSH
- benzoáty terapeutické užití MeSH
- dospělí MeSH
- glykemický clamp MeSH
- hypoglykemika terapeutické užití MeSH
- inhibitory ACE terapeutické užití MeSH
- inzulin terapeutické užití MeSH
- inzulinová rezistence fyziologie MeSH
- krevní glukóza účinky léků metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom krev farmakoterapie MeSH
- porucha glukózové tolerance krev farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
We evaluated the utility of impaired fasting plasma glucose as defined by ADA to identify women with polycystic ovary syndrome (PCOS) affected by impaired glucose metabolism (i.e. impaired fasting glucose, impaired glucose tolerance and diabetes mellitus). In 330 women with PCOS, according to ESHRE criteria, an oral glucose tolerance test was done. Impaired fasting glucose was present in 36 women (12%), impaired glucose tolerance in 29 women (8.8%) and diabetes mellitus in 10 women (3%), 4 of them have fasting glucose higher than 7 mmol/l. The combination of impaired fasting glucose and impaired glucose tolerance was seen in 5 women (1.5%). The sensitivity of impaired fasting glucose for the detection of impaired glucose tolerance was 24% and specificity 91.8%. When fasting glucose above 5.6 mmol/l was used as the screening criterion, 28/35 subjects (80%) would have been missed. We conclude that fasting plasma glucose is not sufficiently sensitive for the detection of impaired glucose tolerance and diabetes mellitus type 2 in women with PCOS.
- MeSH
- dospělí MeSH
- glukózový toleranční test MeSH
- krevní glukóza metabolismus MeSH
- lidé MeSH
- mladý dospělý MeSH
- omezení příjmu potravy krev MeSH
- poruchy metabolismu glukózy komplikace diagnóza MeSH
- retrospektivní studie MeSH
- syndrom polycystických ovarií krev komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Insulin resistance (IR) is the result of long-lasting positive energy balance and the imbalance between the uptake of energy rich substrates (glucose, lipids) and energy output. The defects in the metabolism of glucose in IR and type 2 diabetes are closely associated with the disturbances in the metabolism of lipids. In this review, we have summarized the evidence indicating that one of the important mechanisms underlying the development of IR is the impaired ability of skeletal muscle to oxidize fatty acids as a consequence of elevated glucose oxidation in the situation of hyperglycemia and hyperinsulinemia and the impaired ability to switch easily between glucose and fat oxidation in response to homeostatic signals. The decreased fat oxidation results into the accumulation of intermediates of fatty acid metabolism that are supposed to interfere with the insulin signaling cascade and in consequence negatively influence the glucose utilization. Pathologically elevated fatty acid concentration in serum is now accepted as an important risk factor leading to IR. Adipose tissue plays a crucial role in the regulation of fatty acid homeostasis. The adipose tissue may be the primary site where the early metabolic disturbances leading to the development of IR take place and the development of IR in other tissues follows. In this review we present recent evidence of mutual interaction between skeletal muscle and adipose tissue in the establishment of IR and type 2 diabetes.
- MeSH
- acylkoenzym A metabolismus MeSH
- diabetes mellitus 2. typu enzymologie etiologie metabolismus MeSH
- financování vládou MeSH
- inzulinová rezistence fyziologie imunologie MeSH
- kosterní svaly enzymologie metabolismus MeSH
- lidé MeSH
- mastné kyseliny metabolismus MeSH
- poruchy metabolismu glukózy etiologie komplikace MeSH
- tuková tkáň enzymologie metabolismus patofyziologie MeSH
- Check Tag
- lidé MeSH
BACKGROUND: Although evidence indicates that Type II Diabetes is related to abnormal brain aging, the influence of elevated blood glucose on long-term cognitive change is unclear. In addition, the relationship between diet-based glycemic load and cognitive aging has not been extensively studied. The focus of this study was to investigate the influence of diet-based glycemic load and blood glucose on cognitive aging in older adults followed for up to 16 years. METHODS: Eight-hundred and thirty-eight cognitively healthy adults aged ≥50 years (M = 63.1, SD = 8.3) from the Swedish Adoption/Twin Study of Aging were studied. Mixed effects growth models were utilized to assess overall performance and change in general cognitive functioning, perceptual speed, memory, verbal ability, and spatial ability as a function of baseline blood glucose and diet-based glycemic load. RESULTS: High blood glucose was related to poorer overall performance on perceptual speed as well as greater rates of decline in general cognitive ability, perceptual speed, verbal ability, and spatial ability. Diet-based glycemic load was related to poorer overall performance in perceptual speed and spatial ability. CONCLUSION: Diet-based glycemic load and, in particular, elevated blood glucose appear important for cognitive performance/cognitive aging. Blood glucose control (perhaps through low glycemic load diets) may be an important target in the detection and prevention of age-related cognitive decline.
- MeSH
- biologické markery krev MeSH
- dieta s omezením sacharidů MeSH
- dietní sacharidy aplikace a dávkování metabolismus MeSH
- glykemický index * MeSH
- kognice * MeSH
- kognitivní dysfunkce krev etiologie prevence a kontrola MeSH
- krevní glukóza metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- stárnutí * psychologie MeSH
- zdravotnické přehledy MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Švédsko MeSH
Epinephrine controls many important and sometimes opposite processes. This pleiotropic effect is achieved via coupling to different receptor/effector systems. In epididymal white adipose tissue (EWAT) of Wistar rats, we showed that epinephrine stimulated protein kinase B (PKB) phosphorylation on Ser(473). Epinephrine further increased the glucose incorporation into glyceride-glycerol without decreasing glucose availability for other metabolic pathways (i.e. lactate production). Wortmannin (phosphatidylinositol 3-kinase inhibitor) treatment significantly decreased glucose incorporation into glyceride-glycerol and elevated the epinephrine-induced release of free fatty acids (FFA) from the adipose tissue without any change in the intensity of lipolysis measured as glycerol release. Using specific cyclic adenosine monophosphate (cAMP) analogs we demonstrated that cAMP-protein kinase A (PKA) signalling resulted in a strong PKB dephosphorylation and significantly lowered the glucose availability in EWAT. Specific activation of the Epac (exchange protein activated by cAMP)-dependent pathway had only a moderately negative effect on PKB phosphorylation and glucose metabolism. In contrast, α(1) agonist methoxamine increased PKB phosphorylation and lactate production. This effect of methoxamine was additive to the effect of insulin and it was abolished by wortmannin treatment. In EWAT of spontaneously dyslipidemic hereditary hypertriglyceridemic (HHTg) rats, we demonstrated significantly lower epinephrine-induced glucose utilization but higher sensitivity to its lipolytic effect. We conclude that in EWAT, epinephrine controls two opposite processes (FFA release and FFA retention) via two different effector systems. The impairment of α(1)-dependent, epinephrine-stimulated, glycolysis-dependent FFA esterification may contribute to the establishment of dyslipidemia in insulin resistance.
- MeSH
- adrenalin metabolismus MeSH
- alfa-adrenergní receptory metabolismus MeSH
- AMP cyklický metabolismus MeSH
- beta-adrenergní receptory metabolismus MeSH
- biologické modely MeSH
- fosforylace MeSH
- glukosa metabolismus MeSH
- krysa rodu rattus MeSH
- kyseliny mastné neesterifikované krev metabolismus MeSH
- metabolický syndrom metabolismus MeSH
- proteinkinasy závislé na cyklickém AMP metabolismus MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- signální transdukce MeSH
- tuková tkáň metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Strenuous exercise induces delayed-onset muscle damage including oxidative damage of cellular components. Oxidative stress to muscle cells impairs glucose uptake via disturbance of insulin signaling pathway. We investigated glucose uptake and insulin signaling in relation to oxidative protein modification in muscle after acute strenuous exercise. ICR mice were divided into sedentary and exercise groups. Mice in the exercise group performed downhill running exercise at 30 m/min for 30 min. At 24 hr after exercise, metabolic performance and insulin-signaling proteins in muscle tissues were examined. In whole body indirect calorimetry, carbohydrate utilization was decreased in the exercised mice along with reduction of the respiratory exchange ratio compared to the rested control mice. Insulin-stimulated uptake of 2-deoxy-[3H]glucose in damaged muscle was decreased after acute exercise. Tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidyl-3-kinase/Akt signaling were impaired by exercise, leading to inhibition of the membrane translocation of glucose transporter 4. We also found that acute exercise caused 4-hydroxy-nonenal modification of IRS-1 along with elevation of oxidative stress in muscle tissue. Impairment of insulin-induced glucose uptake into damaged muscle after strenuous exercise would be related to disturbance of insulin signal transduction by oxidative modification of IRS-1.
- MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- glukosa metabolismus MeSH
- inzulin metabolismus MeSH
- kondiční příprava zvířat MeSH
- kosterní svaly metabolismus MeSH
- myši inbrední ICR MeSH
- myši MeSH
- oxidace-redukce MeSH
- oxidační stres MeSH
- přenašeč glukosy typ 4 metabolismus MeSH
- proteiny insulinového receptorového substrátu metabolismus MeSH
- protoonkogenní proteiny c-akt metabolismus MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
