It is now generally accepted that adipose tissue acts as an endocrine organ producing a number of substances with an important role in the regulation of food intake, energy expenditure and a series of metabolic processes. Adiponectin is a recently discovered protein produced exclusively by adipocytes. A number of studies have shown that obesity, insulin resistance and atherosclerosis are accompanied by decreased adiponectin levels and that adiponectin replacement under experimental settings is able to diminish both insulin resistance and atherosclerosis. The aim of this review is to summarize the current knowledge about the physiology and pathophysiology of adiponectin and to discuss its potential in the treatment of insulin resistance and atherosclerosis.
Close links between hypertension, hypertriglyceridemia, insulin resistance and other symptoms of metabolic syndrome was demonstrated in humans and experimental animals. Quantitative trait loci for defects in glucose and fatty acid metabolism, hypertriglyceridemia and hypertension were mapped in spontaneously hypertensive rats (SHR) on chromosome 4 and defective Cd36 gene was identified in this region. Here we investigated the polymorphism of Cd36 gene in Prague hereditary hypertriglyceridemic (HTG) rats, which represent another model of genetic hypertension and metabolic syndrome. These animals were compared with NIH-derived SHR and two different normotensive control strains (WKY, LEW). In spite of the fact that HTG and SHR rats had similar metabolic disturbances, genotype analysis of PCR products has shown that Cd36 mutation was not present in HTG rats. In conclusion, we have revealed that defective Cd36 is probably a candidate gene for disorded fatty-acid metabolism, glucose intolerance and insulin resistance in NIH-derived SHR, but other genes might play a role in pathogenesis of metabolic syndrome in Prague hereditary hypertriglyceridemic rats. This is in accordance with the absence of defective Cd36 gene in original SHR from Japan.
We investigated the potential role of magnesium (Mg) dysbalance in the pathogenesis of insulin resistance (IR) in patients with mildly-to-moderately decreased renal function (creatinine: 142.8±11.0 mmol/l). The data were compared to those of 8 age- and sex-matched healthy controls (CTRL). The standard oral glucose tolerance test (oGTT) was performed in 61 patients. Twenty-two patients were classified as IR according to their values on fasting and after-load immunoreactive insulin concentrations. Serum and total erythrocyte Mg (tErMg) (atomic absorption spectro-photometry) and free erythrocyte Mg (fErMg) concentrations (31P NMR spectroscopy) were determined prior to and two hours after the glucose load. Ten out of 39 insulin-sensitive (IS) patients, but only one out of 22 insulin-resistant (IR) patients, had a low basal fErMg concentration (<162.2 mmol/l, c2, p<0.01). IR patients had higher serum Mg, total erythrocyte Mg and bound erythrocyte Mg (bErMg) concentrations (both before and after glucose load) when compared with the IS group. Both groups responded to the glucose load with a significant decrease in serum Mg concentration (within the normal range), while the IR group also exhibited a decline in tErMg and bErMg. The mean sum of insulin needed to metabolize the same glucose load correlated positively with tErMg (r=0.545, p<0.01) and bErMg (r=0.560, p<0.01) in the IR patients. It is concluded that, at an early stage of renal dysfunction, IR is not associated with the decline in free erythrocyte Mg concentration, but the magnesium handling in red blood cells is altered., K. Šebeková, K. Štefíková, D. Polakovičová, V. Spustová, R. Dzúrik., and Obsahuje bibliografii
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.
Hypertriglyceridemia and hypertension seem to be very important cardiovascular risk factors. The Prague hereditary hypertriglyceridemic (hHTG) rat was developed as a model of human hypertriglyceridemia. It was demonstrated that these rats are not obese, they are hypertensive and insulin resistant and they have some disturbances in glucose
metabolism. Several QTLs were identified for blood pressure, its particular components (dependent on major vasoactive systems) and plasma triglycerides throughout the genome of hHTG rats by using of F2 hybrids strategy. It is evident that hHTG rats are a suitable model for the study of metabolic disturbances in relation to blood pressure as well as for the
search of genetic determinants of these abnormalities. Numerous abnormalities of blood pressure regulation as well as alterations in the structure and function of cardiovascular apparatus (heart, conduit and resistance arteries) were found in hHTG rats. A special attention was paid to possible changes in the efficiency of various vasoactive systems such as
nitric oxide, renin-angiotensin-aldosterone system and sympathetic nervous system, which seem to contribute substantially to cardiovascular and/or metabolic abnormalities observed in Prague hereditary hypertriglyceridemic rats.
The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. Impaired vasodilator reactivity has been recognized as an early hemodynamic abnormality in obese patients, but also increased vasoconstrictor tone importantly contributes to their vascular damage. In particular, upregulation of the endothelin (ET)-1 system, consistently reported in these patients, might accelerate atherosclerosis and its complication, given the pro-inflammatory and mitogenic properties of ET-1. In recent years, a number of gut hormones, in addition to their role as modulators of food intake, energy balance, glucose and lipid metabolism, and insulin secretion and action, have demonstrated favorable vascular actions. They increase the bioavailability of vasodilator mediators like nitric oxide, but they have also been shown to inhibit the ET-1 system. These features make gut hormones promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant advantages. Therefore, there is real hope that better understanding of the properties of gut-derived substances might provide more effective therapies for the obesity-related cardiometabolic syndrome., F. Schinzari, M. Tesauro, C. Cardillo., and Seznam literatury
Obstructive sleep apnoea (OSA) has been associated with disturbances in energy metabolism and insulin resistance,nevertheless, the links between OSA severity, resting energy expenditure (REE) and insulin resistance (homeostasis model assessment, HOMA-IR) remained unexplored Therefore, we investigates the effects of OSA severity on REE, and relationships between REE and HOMA-IR in patients with OSA. Forty men[mean (SD) age 49.4 (11.4) years] underwent overnight polysomnography; REE was assessed using indirect calorimetry. REE adjusted for fat -free mass (FFM) was higher in patients with moderate-to severe OSA [n=24; body mass index (BMI) 31.1(2.7) kg.m-2; apnoea-hypopnoea index (AHI) ≥15 episodes.h-1] compared to participants with no clinically significant OSA(n=16; BMI 30.3 (2.2) kg.m-2; AHI<15 episodes.h-1) [median (interquartile range) 30.4 (26.1-31.3) versus 25.8 (24.6-27.3) kcal.kg-1.24 h-1, p=0.005)]. AHI and oxygen desaturation index(ODI) were directly related to REE/FFM (p=0.001; p<0.001, respectively) and to HOMA-IR (p<0.001 for both). In stepwise multiple linea models,REE/FFM was independently predicted by ODI (p<0.001) and age(p=0.028) (R2=0.346); HOMA-IR wasindependently predicted by ODI only (p<0.001,R2=0.457). In conclusion, male patients with moderate-to severe OSA haveincreased REE paralleled by impaired insulin sensitivity. Severity of nocturnal intermittent hypoxia reflected by ODI is an independent predictor of REE/FFM and HOMA-IR.
This study was performed to test whether plasma homocysteine concentrations are related to insulin resistance in healthy premenopausal women. For this purpose, the relationship between insulin resistance (as assessed by HOMA index) and fasting plasma homocysteine level was determined in 83 healthy volunteers. The results indicated that homocysteine concentrations did not vary as a function of HOMA index (r = -0.147). Plasma homocysteine concentrations also did not vary as a function of other parameters of insulin resistance such as HDL-cholesterol and triglycerides, which they correlated inversely with body mass index (BMI). Furthermore, when individuals were classified according to quartiles of insulin resistance (HOMA index), plasma homocysteine concentrations from the lowest to the highest quartiles were not significantly different. On the other hand, the HOMA index correlated significantly with triglyceride concentrations (r = 0.377, p< 0.001), HDL-cholesterol (r = -0.310, p< 0.01) and BMI (r = 0.468, p< 0.001). These results suggest that plasma homocysteine concentrations are not related to insulin resistance and/or metabolic abnormalities associated with it in premenopausal women.
Spexin (SPX) and kisspeptin (KISS) are novel peptides relevant in the context of regulation of metabolism, food intake, puberty and reproduction. Here, we studied changes of serum SPX and KISS levels in female non-obese volunteers (BMI<25 kg/m2) and obese patients (BMI>35 kg/m2). Correlations between SPX or KISS with BMI, McAuley index, QUICKI, HOMA IR, serum levels of insulin, glucagon, leptin, adiponectin, orexin-A, obestatin, ghrelin and GLP-1 were assessed. Obese patients had lower SPX and KISS levels as compared to non-obese volunteers (SPX: 4.48±0.19 ng/ml vs. 6.63±0.29 ng/ml; p<0.001, KISS: 1.357±0.15 nmol/l vs. 2.165±0.174 nmol/l; p<0.01). SPX negatively correlated with BMI, HOMA-IR, insulin, glucagon, active ghrelin and leptin. Positive correlations were found between SPX and QUICKI index, McAuley index, serum levels of obestatin, GLP-1 and adiponectin and orexin-A Serum KISS negatively correlated with BMI, HOMA-IR, serum levels of insulin, glucagon, active ghrelin and leptin. KISS positively correlated with QUICKI index, McAuley index and adiponectin. In summary, SPX and KISS show negative correlations with obesity, insulin resistance indices, and hormones known to affect insulin sensitivity in females. Both, SPX and KISS could be therefore relevant in the pathophysiology of obesity and insulin resistance., P. A. Kołodziejski, E. Pruszyńska-Oszmałek, E. Korek, M. Sassek, D. Szczepankiewicz, P. Kaczmarek, L. Nogowski, P. Maćkowiak, K. W. Nowak, H. Krauss, M. Z. Strowski., and Seznam literatury
Mild hyperhomocysteinemia has been established as a new independent risk factor for atherosclerosis and thrombosis. The metabolic syndrome of insulin resistance is associated with a high risk of coronary heart disease. Our objective was to determine if any relationship exists between the metabolic syndrome of insulin resistance in non-diabetic subjects and total serum homocysteine levels. Sixty-six healthy volunteers (33 males and 33 females) were selected from the population of Pilsen. Insulin resistance was measured by the Insulin Suppression Test using Octreotide. Steady-state plasma glucose concentrations at the end of the test period provided a quantitative measure of insulin resistance. Serum homocysteine level was estimated by high-pressure liquid chromatography. Serum folate and vitamin B12 were estimated using commercial kits on an Abbott IMx analyzer. All other laboratory tests were performed by standard methods in a routine biochemical laboratory. Subjects with the highest tertile of steady-state plasma glucose showed a significantly higher body mass index, blood pressure, fasting plasma triglyceride levels, plasminogen activator inhibitor-1 and lower HDL-cholesterol, i.e. an insulin resistance pattern. These subjects had significantly lower serum homocysteine levels compared with non-insulin resistant subjects. The negative association of insulin resistance and serum homocysteine was unexpected. The contribution of plasma folate levels to serum homocysteine levels and serum creatinine was significantly negative and positive, respectively., H. Rosolová, J. Šimon, O. Mayer Jr., J. Racek, T. Dierzé, D. W. Jacobsen., and Obsahuje bibliografii