Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some experimental and clinical studies were done from the metabolic viewpoint to elucidate the characteristics of myonephropathic-metabolic syndrome. In experimental dogs with their femoral arteries ligated and two third of femoral muscles divided, aldolase and myoglobin showed remarkable increase without significant changes in electrolytes. Slight increase of GPT and GOT was observed. Amino acids showed elevation in urea, taurin, leucin, isoleucin, valine, threonine, 3-methylhistidine, phenylalanine, histidine, lysine, methionine, tyrosine and anserin and decrease in glutamine, alanine, glycine, proline, carnosine, citrullin and arginine. In patients with acute arterial occlusion, potassium, GOT, LDH, CPK, lactate and pyruvate increased moderately and myoglobin showed remarkable increase and aldolase slight increase. Amino acids showed remarkable increase in 3-methylhistidine and beta-amino-isobutyric acid and moderate increase in phenylalanine and arginine. These results revealed that measurement of free amino acid concentration, especially that of methylhistidine as well as myoglobin, pyruvate, lactate and some other enzymes might be of great help to predict the prognosis of patients with acute arterial occlusion of the extremities.
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PMID:[Metabolic study on acute arterial occlusion of the extremities]. 667 89

In type 2 diabetes, the threonine (Thr) for alanine (Ala) codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with elevated fasting and postprandial triglycerides and dyslipidemia when compared with the wild type (Ala-54/Ala-54). To assess whether this is the case in patients with type 1 diabetes, who usually do not manifest the metabolic syndrome, we screened 181 patients with similar glycemic control as the type 2 patients. Thirty percent were heterozygous, and 9% were homozygous for the polymorphism. Mean (+/-SEM) fasting plasma triglyceride levels in patients with the wild type (n = 84), those heterozygous for Ala-54/Thr-54 (n = 44), and those homozygous for the Thr-54 (n = 13) were 1.0 +/- 0.07, 1.1 +/- 0.17, and 1.2 +/- 0.23 mmol/liter, respectively. In addition, there were no differences in total, low-density lipoprotein, high-density lipoprotein, and non-high density lipoprotein cholesterol among the three groups. After a fat load, the postprandial area under the curve of triglyceride in plasma, chylomicrons, and very low-density lipoprotein were similar between the wild type (n = 18) and the Thr-54 homozygotes (n = 12). In conclusion, in contrast to type 2, type 1 diabetes does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene to cause hypertriglyceridemia/dyslipidemia. Insulin resistance could account possibly for this difference.
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PMID:Unlike type 2 diabetes, type 1 does not interact with the codon 54 polymorphism of the fatty acid binding protein 2 gene. 1216 3

Fatty liver at ultrasounds, with/ without raised plasma levels of hepatic enzymes, is common in obesity. In most cases, it is the hallmark of non-alcoholic fatty liver disease (NAFLD), a potentially progressive disease associated with insulin resistance and the metabolic syndrome (MS). We tested the hypothesis that insulin resistance per se might be associated with hepatocellular necrosis. Alanine and aspartate aminotransferases (ALT and AST; no.=799) and gamma-glutamyltranspeptidase (GGT; no.=459) were analyzed in a group of treatment-seeking obese patients recruited in 12 Italian medical centers. Insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR; no.=522). Median ALT and AST increased with increasing obesity class (p=0.001 and p=0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased with the obesity class (p<0.0001), and was higher in subjects with elevated ALT (median, 4.93 vs 2.89; p<0.0001). A significant correlation was observed between HOMA-IR and ALT (R2=0.208; p<0.0001), as well as between HOMA-IR and AST or GGT (R2=0.112 and R2=0.080; p<0.0001). The correlation was maintained when cases with elevated enzyme levels were omitted from analysis. Diabetes and hypertriglyceridemia were the features of the MS most commonly associated with raised liver enzymes. In logistic regression, after correction for age, gender, BMI and features of the MS, HOMA-IR maintained a highly predictive value for raised ALT, AST and GGT. We conclude that in obesity insulin resistance is a risk factor for raised liver enzyme levels, possibly related to NAFLD.
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PMID:Aminotransferase and gamma-glutamyltranspeptidase levels in obesity are associated with insulin resistance and the metabolic syndrome. 1596 6

The alanine (A) to threonine (T) substitution at codon 54 of the intestinal fatty acid-binding protein 2 (FABP2) has been associated with dyslipidaemia and other characteristics of the metabolic syndrome, which in turn is a risk factor for cerebrovascular disease. The aim of this study was to investigate whether the A54T polymorphism in the FABP2 gene is associated with internal carotid artery (ICA) stenosis in stroke patients. Swedish subjects initially diagnosed with acute cerebrovascular disease (n=196) that had been assessed with ultrasound of the carotid arteries were identified and grouped depending on whether a stenosis was found. The subjects were genotyped for the A54T polymorphism using a PCR-RFLP method. In a multivariate logistic-regression analysis, where known risk factors for atherosclerosis were fixed (diabetes, systolic blood pressure, age and smoking), having the FABP2 T allele was a significant risk factor for ICA stenosis (odds ratio 2.9; 95% confidence interval, 1.1-7.7; p = 0.04) together with diabetes (odds ratio 4.9; 95% confidence interval, 1.8-14; p < 0.01). Age, smoking and blood pressure did not reach statistical significance. In conclusion, our result supports the hypothesis that the FABP2 A54T polymorphism is associated with ICA stenosis.
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PMID:Genetic variation of the intestinal fatty acid-binding protein 2 gene in carotid atherosclerosis. 1601 94

Our objective was to search for differences in genotypes of peroxisome proliferator-activated receptor gamma (PPARgamma) (Pro12 Ala) and its coactivator PGC-1alpha (Gly482 Ser) in adolescents harboring features of metabolic syndrome. In a population-based study, we determined medical history, anthropometric variables, biochemical measurements and arterial blood pressures of 934 high-school students of Caucasian origin. We selected 220 adolescents who had systolic or diastolic blood pressures more than the 80th or less than the 20th percentiles based on the previous single set of measurements. One hundred and seventy-five adolescents completed the study and underwent two additional blood pressure measurements on different days, as well as biochemical analysis and genotyping. We found no association between insulin resistance, body mass index (BMI) and leptin levels and PPARgamma and PGC-1alpha genotypes. The 12 Ala PPARgamma allele was associated with increased waist-to-hip ratio (WHR) and carriers seemed to have higher diastolic blood pressure and lower pulse pressure than non-carriers, particularly in the hypertensive and overweight group. Although Ser482 Ser PGC-1alpha homozygotes had lower WHRs than other PGC-1alpha genotypes, they were more frequent in the hypertensive group than in the normotensive (44.4 vs 24.5%, P<0.03), so the 482 Ser PGC-1 allele was in our population a risk factor for hypertension independently of WHR, homeostasis model assessment of insulin resistance, BMI and Pro12 Ala PPARgamma variant (odds ratio=4.0, 95% confidence interval 1.5-10.6, P<0.01). Multiple regression analysis showed that age- and sex-adjusted systolic blood pressure correlated with the 482 Ser PGC-1 allele regardless of those covariates. In conclusion, the Gly482 Ser variant of the PGC-1alpha gene may be an independent genetic risk factor for young-onset hypertension.
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PMID:Peroxisome proliferator-activated receptor gamma and its coactivator-1 alpha may be associated with features of the metabolic syndrome in adolescents. 1621 16

Elevated plasma homocysteine has been reported in individuals with diseases of the metabolic syndrome including vascular disease and insulin resistance. As homocysteine exerts detrimental effects on endothelial and neuronal cells, this study investigated effects of acute homocysteine exposure on beta-cell function and insulin secretion using clonal BRIN-BD11 beta-cells. Acute insulin release studies in the presence of various test reagents were performed using monolayers of BRIN-BD11 cells and samples assayed by insulin radioimmunoassay. Cellular glucose metabolism was assessed by nuclear magnetic resonance (NMR) analysis following 60-min exposure of BRIN-BD11 cell monolayers to glucose in either the absence or presence of homocysteine. Homocysteine dose-dependently inhibited insulin release at moderate and stimulatory glucose concentrations. This inhibitory effect was reversible at all but the highest concentration of homocysteine. 13C-glucose NMR demonstrated decreased labelling of glutamate from glucose at positions C2, C3 and C4, indicating that the tricarboxylic acid (TCA) cycle-dependent glucose metabolism was reduced in the presence of homocysteine. Homocysteine also dose-dependently inhibited insulinotropic responses to a range of glucose-dependent secretagogues including nutrients (alanine, arginine, 2-ketoisocaproate), hormones (glucagon-like peptide-1 (7-36)amide, gastric inhibitory polypeptide and cholecystokinin-8), neurotransmitter (carbachol), drug (tolbutamide) as well as a depolarising concentration of KCl or elevated Ca2+. Insulin secretion induced by activation of adenylate cyclase and protein kinase C pathways with forskolin and phorbol 12-myristate 13-acetate were also inhibited by homocysteine. These effects were not associated with any adverse action on cellular insulin content or cell viability, and there was no increase in apoptosis/necrosis following exposure to homocysteine. These data indicate that homocysteine impairs insulin secretion through alterations in beta-cell glucose metabolism and generation of key stimulus-secretion coupling factors. The participation of homocysteine in possible beta-cell demise merits further investigation.
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PMID:Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic beta-cell glucose metabolism and insulin secretion. 1664 97

The mobilization of triacylglycerides from storage in adipocytes to the liver is a vital response to the fasting state in mammalian metabolism. This is accompanied by a rapid translational activation of genes encoding mitochondrial, microsomal, and peroxisomal beta-oxidation in the liver, in part under the regulation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha). A failure to express PPAR-alpha results in profound metabolic perturbations in muscle tissue as well as the liver. These changes represent a number of deficits that accompany diabetes, dyslipidemia, and the metabolic syndrome. In this study, the metabolic role of PPAR-alpha has been investigated in heart, skeletal muscle, liver, and adipose tissue of PPAR-alpha null mice at 1 mo of age using metabolomics. To maximize the coverage of the metabolome in these tissues, (1)H-NMR spectroscopy, magic angle spinning (1)H-NMR spectroscopy, gas chromatography-mass spectrometry, and liquid chromatography-mass spectrometry were used to examine metabolites in aqueous tissue extracts and intact tissue. The data were analyzed by the multivariate approaches of principal components analysis and partial least squares. Across all tissues, there was a profound decrease in glucose and a number of amino acids, including glutamine and alanine, and an increase in lactate, demonstrating that a failure to express PPAR-alpha results in perturbations in glycolysis, the citric acid cycle, and gluconeogenesis. Furthermore, despite PPAR-alpha being weakly expressed in adipose tissue, a profound metabolic perturbation was detected in this tissue.
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PMID:A combined 1H-NMR spectroscopy- and mass spectrometry-based metabolomic study of the PPAR-alpha null mutant mouse defines profound systemic changes in metabolism linked to the metabolic syndrome. 1686 74

Although evidence suggests the link between chronic inflammation and oxidative stress as the main mechanism responsible for endothelial dysfunction and cardiovascular complications in patients with metabolic syndrome, little is known about the determining role of each metabolic syndrome component in such alterations. This study investigated the relation between systemic oxidative alterations and metabolic syndrome features in 41 patients. Compared with control subjects, serum vitamin C and alpha-tocopherol concentrations were lower and those of lipid peroxides [thiobarbituric acid reactive substances (TBARs)] were higher in metabolic syndrome patients (P < 0.001). A linear relation was observed between visceral fat thickness and serum TBARs:cholesterol ratio (r = 0.541, P < 0.001), whereas negative correlations were found between alpha-tocopherol and BMI (r = -0.212, P < 0.05) and the grade of liver steatosis (r = -0.263, P < 0.02). Patients with metabolic syndrome and liver steatosis had higher serum hyaluronate (HA) concentrations (P < 0.001). Serum HA was positively correlated with serum alanine amino transferase (r = 0.715, P < 0.001) and the homeostasis monitoring assessment index (r = 0.248, P < 0.03). The presence of metabolic syndrome was predicted from a linear combination of visceral fat and all oxidative variables. In metabolic syndrome patients, serum nitrosothiols and vitamin C concentrations, which were lower (P < 0.001) than in control subjects, were inversely related to the grade of hypertension (r = -0.645, P < 0.001 and r = -0.415, P < 0.007, respectively). In conclusion, metabolic syndrome patients exhibited decreased antioxidant protection and increased lipid peroxidation. Our results indicate a strong association between increased abdominal fat storage, liver steatosis, and systemic oxidative alterations in metabolic syndrome patients and diminished nitrosothiols and vitamin C concentrations as important factors associated with hypertension in these patients.
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PMID:Systemic oxidative alterations are associated with visceral adiposity and liver steatosis in patients with metabolic syndrome. 1711 14

Association of low sex hormone-binding globulin (SHBG) level with the risk of the metabolic syndrome (MetS) in men has previously been reported. A proline to alanine substitution in codon 12 of the peroxisome proliferator activated receptor gamma 2 (PPARgamma2) gene has been shown to be related to high insulin sensitivity. The relationship of SHBG levels with the Pro12Ala polymorphism of PPARgamma2 in men has not been previously studied. Therefore, we investigated the effect of the Pro12Ala polymorphism of PPARgamma2 on SHBG levels in 202 young Finnish men. The range of SHBG was from 3.30 to 73 nmol/L (geometric mean = 17.90; 95%CI = 16.62-19.25 nmol/L). Baseline SHBG levels tended to be lower in men who developed the MetS (n = 11) compared to men who did not develop the MetS (n = 169) (22.85 vs 17.26 nmol/L) on a high-caloric diet during their 6 mo military service. SHBG levels tended to be higher among the subjects with the Ala12Ala genotype compared to subjects with the Pro12Pro or Pro12Ala genotypes of the PPARgamma gene (27.7 vs 21.7 and 22.7 nmol/L). Among the carriers of the Pro12Pro genotype, those who developed the MetS (n = 8) had significantly lower levels of SHBG compared to men who did not develop the MetS (n = 93) (13.23 vs 24.22 nmol/L, p = 0.027). Among the subjects who developed the MetS those with the Pro12Pro genotype (n = 3) had significantly lower levels of SHBG compared to subjects with X12Ala (n = 8) (13.23 vs 28 nmol/L, p = 0.025). We conclude that the 12Ala allele of PPARgamma2 may influence SHBG levels in young Finnish men.
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PMID:The Pro12Ala polymorphism of the PPAR gamma 2 gene influences sex hormone-binding globulin level and its relationship to the development of the metabolic syndrome in young Finnish men. 1732 77

In a population-based sample, after excluding alcohol consumption, hepatotoxic drugs and hepatitis B and C infected, we investigated if alanine-aminotransferase (ALT) was associated with metabolic syndrome and insulin resistance, and if this association was caused by non-alcoholic fatty liver disease (NAFLD). The sample (432 female and 119 male) was divided into two ALT thresholds corresponding to the 50th and 75th percentiles (P) (female > or = 15 and > or = 19 U/L; male > or = 17 and > or = 23 U/I, respectively). Blood pressure, body mass index, waist circumference, cholesterol, HDL cholesterol (HDLc), triglyceride (TG), TG/HDLc ratio, glycemia and homeostasis model assessment of insulin resistance (HOMA-IR) were compared between those above and below each ALT threshold. Female placed above the 50th P of ALT had higher levels of TG/HDLc ratio (p=0.029), glycemia (p=0.028), and homeostasis model assessment of insulin resistance, (p=0.045), and above the 75th P had higher SBP (p=0.036), DBP (p=0.018), TG (p=0.024), TG/HDLc ratio (p=0.028), glycemia (p=0.004) and HOMA-IR (p=0.0014). Male placed above the 50th P of ALT had higher BMI (p=0.017) and TG/HDLc ratio (p=0.048), and above the 75th P had lower values of HDLc (p=0.042). Only 16.5% of women and 14.5% of men, above the 75th P of ALT, showed an increase in liver brightness in the echography. This work shows in woman an early association of ALT with TG/HDLc ratio and HOMA-IR. Since the last two are independent predictors of cardiovascular risk, attention should be drawn to ALT values near the upper limit of the normal range even in the absence of NAFLD and obesity.
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PMID:Alanine-aminotransferase: an early marker for insulin resistance? 1759 95


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