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)

The present status of knowledge about glucagon pathophysiology in diabetes is reviewed. 1) A-cells behave abnormally in all varieties of diabetes mellitus, spontaneous and experimental, except perhaps in case of pancreatectomized humans. These abnormalities are : hyperreactivity of A-cells to arginine, non suppressibility by glucose, and absence of stimulation following hypoglycemia. 2) These abnormalities appear as secondary in most instances : a) A-cells behave in a normal way in most studies with prediabetics ; b) plasma glucagon concentration is normalized by excellent control of diabetes or following prolonged insulin infusion. High doses of insulin are required most of the times to obtain a normalization of A-cell function : in insulin-dependent diabetics, the physiological portoperipheral insulin gradient no longer exists, and the high doses of insulin which are necessary may be the only mean to reconstitute the high insulin concentrations supposed to be present at the A-cell level. 3) Conflicting results have been collected about the role of this glucagon excess in aggravating the diabetic metabolic syndrome. Evanescent effects follow sustained glucagon infusions: but in diabetics, glucagon bursts rather than permanent hyperglucagonemia are observed and these appear deleterious to glucose tolerance. It seems clear however that insulin deprivation is required for the full expression of the consequences of glucagon excess.
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PMID:Glucagon and diabetes mellitus. 37 65

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

Hypertension which is part of the metabolic syndrome has frequently a family background. The authors investigated therefore indicators of insulin sensitivity by the method of a hyperinsulinaemic euglycaemic clamp in the offspring of hypertensive probands. In conjunction with the increased interest in the role of muscles in influencing insulin sensitivity the authors were also interested in serum amino acid levels. They examined a group of 15 healthy offspring of hypertonic subjects (PHT) and compared them with a group of 18 healthy volunteers without a family-history of hypertension. PHT had as compared with controls a higher systolic pressure (117 +/- 7.2 mm Hg vs. 106.1 +/- 11.7 mm Hg p < 0.01). In the clamp examination in PHT significantly lower indexes of tissue insulin sensitivity were recorded, SI (46.51 +/- 11.8% vs. 54.3 +/- 7.79%, p = 0.02) and ISI (6.6 +/- 3.99 vs. 9.88 +/- 5.05, p < 0.01). In the PHT group were, in addition to the different ratio of some branched chain amino acids and tyrosine, also relations between indicators of insulin sensitivity and arginine. It is thus obvious that signs of reduced insulin sensitivity are present in PHT already in the preclinical stage. Relations between the altered insulin sensitivity and arginine, the precursor of nitrogen oxide, apparent only in PHT could be a stimulus for seeking associations with endothelial damage described in insulin resistant conditions.
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PMID:[Relation between serum amino acids and insulin sensitivity (results of a clamp study in offspring of hypertensive patients]. 960 33

Patients with metabolic syndrome represent a group with extensive cardiovascular risk factors for the development of atherosclerosis, which may be preceded by an impairment of endothelial function. Endothelial dysfunction is characterized by a reduced availability of bioactive nitric oxide, the principal mediator of endothelium-dependent vasodilation. In the present study we assessed NO synthesis in vivo by measuring the NO-related amino acids L-arginine and L-citrulline and in particular the stable intermediate compound N(omega)-hydroxy-L-arginine (L-NHA) in patients with metabolic syndrome by using high-performance liquid chromatography (HPLC) analysis. As a prerequisite to our study, we measured the amino acid concentrations in 31 healthy volunteers to investigate gender and age differences. To prove whether blood drawn from peripheral veins reflects plasma concentrations of the whole vessel system, several blood samples from different regions were obtained from patients undergoing elective left and right heart catheterization. In the latter group, no significant differences were noted among the plasma concentrations between the different sample sites. In healthy volunteers, there were no significant differences in plasma concentrations of any one specific amino acid between males and females or age groups. The main finding of the study is that the intermediate product of NO synthesis, L-NHA, is significantly reduced in the plasma samples of patients with a metabolic syndrome as compared with samples from healthy control subjects. The plasma concentrations of the NO precursor L-arginine and the end product of NO synthesis, L-citrulline, were unchanged. In conclusion, our results suggest that plasma levels of L-NHA are independent of age and gender and are not different at various locations within the vascular system. In a group of patients at high risk for the development of atherosclerosis, we found reduced plasma concentrations of L-NHA, either caused by a decreased endothelial NO synthase activity or caused by an increased breakdown of L-NHA by pathways independent of NO synthase, resulting in a reduced availability of L-NHA for NO synthesis.
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PMID:Decreased plasma concentrations of L-hydroxy-arginine as a marker of reduced NO formation in patients with combined cardiovascular risk factors. 1081 Oct 58

The objective of this study was to investigate possible defects in the insulin sensitivity and/or the acute insulin response in a group of Mexican patients displaying early-onset type 2 diabetes and to evaluate the contribution of mutations in three of the genes linked to maturity-onset diabetes of the young. We studied 40 Mexican patients with an age of diagnosis between 20 and 40 yr in which the insulin sensitivity as well as the insulin secretory response were measured using the minimal model approach. A partial screening for possible mutations in 3 of the 5 genes linked to maturity-onset diabetes of the young was carried out by PCR-single strand conformation polymorphism analysis. A low insulin secretory capacity (AIRg = 68.5 +/- 5 muU/mL.min) and a near-normal insulin sensitivity (3.43 +/- 0.2 min/muU.mL x 10(4)) were found in these patients. Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases had insulin resistance; these subjects had the lipid abnormalities seen in the metabolic syndrome. A defect in insulin secretion is the hallmark in Mexican diabetic patients diagnosed between 20 and 40 yr of age. Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. These particular sequence changes have not been previously reported and therefore represent putative new mutations. Even in the absence of endogenous hyperinsulinemia, insulin resistance is associated with an adverse lipid profile.
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PMID:Early-onset type 2 diabetes: metabolic and genetic characterization in the mexican population. 1123 4

Genetic studies in mice have demonstrated a complementary role for the melanocortin-3 receptor (MC3R) and MC4R in the control of energy balance. Knockout of the MC3R in mice revealed an exclusively metabolic syndrome and increased fat mass. In the present study, we found a total of 5 novel single nucleotide polymorphisms (SNPs) of the MC3R gene in the chickens of high weight (HW) and low weight (LW) lines from divergently selected for high or low body weight at 8 weeks of age in White Plymouth Rock. Only one of the 5 SNPs led to amino acid substitution (Leu-->Arg) in HW and LW lines animals: a T/G substitution at nucleotide (nt) position 452 of coding sequence. Three of the 5 SNPs distinguished the birds from HW and LW lines: an A/G substitution at nt position 549 in LW line, an A/G substitution at nt position 882 in HW line, and a C/T substitution at nt position 894 in LW line, respectively. Another SNP was presented only in one of two HW line animals: a C/T substitution at nt position 564. Of the 5 SNPs, only A/G polymorphism at nt position 549 is located within a Dde I restriction enzyme recognition site. We designed a PCR-RFLP test based on the enzyme Dde I and screened the chickens for HW and LW lines' intercross. Analysis of variance revealed a significant influence of the MC3R genotype on body weight in the chickens for both sex and abdominal fat mass in male chickens. The result suggests that the MC3R as a candidate gene can explain significant difference for body weight in the intercross chickens.
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PMID:[Studies of relationship between the melanocortin-3 receptor gene and body weight in chicken for high and low weight lines' intercross]. 1198 65

Insulin resistance is a metabolic syndrome commonly seen in obesity. Leptin, the obese gene product, plays a role in the regulation of cardiac function. Elevated leptin levels have been demonstrated under insulin-resistant states such as obesity and hypertension, although their role in cardiac dysfunction is unknown. This study was designed to determine the impact of prediabetic insulin resistance on leptin levels and leptin-induced cardiac contractile response. Whole-body insulin resistance was generated with a 10-week dietary sucrose feeding. Contractile and intracellular Ca(2+) properties were evaluated in ventricular myocytes using an IonOptix system. The contractile indices analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), maximal velocity of shortening/relengthening (+/-dL/dt), fura-fluorescence intensity change (deltaFFI) and decay rate (tau). Sucrose-fed rats displayed significantly elevated body weight and plasma leptin levels, depressed PS, +/-dL/dt, shortened TPS, prolonged TR(90) and tau, as well as reduced deltaFFI compared to the starch-fed control group. Leptin (1-1000 nM) elicited a concentration-dependent depression of PS and deltaFFI in myocytes from both starch and sucrose groups. Leptin-induced contractile depression was abolished by the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyle ester, elevation of the extracellular Ca(2+) concentration, the Janus activated kinase 2 inhibitor AG-490 or the mitogen activated protein kinase inhibitor SB203580 in myocytes from both sucrose and starch groups. Moreover, AG-490 and SB203580 unmasked a positive response of PS in myocytes from both groups. These data indicate that insulin resistance directly induces hyperleptinemia and cardiac contractile dysfunction, without affecting leptin-mediated cardiac contractile function at the myocyte level.
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PMID:Insulin resistance induces hyperleptinemia, cardiac contractile dysfunction but not cardiac leptin resistance in ventricular myocytes. 1451 67

Endogenous catecholamines contribute to regulation of adipose tissue lipolysis, glucose homeostasis, and vascular tone. The goal of the present study was to assess the association between the Gly(16)-->Arg(16) and Gln(27)-->Glu(27) polymorphisms of the beta(2)-adrenergic receptor and metabolic syndrome. Participants were recruited in a population survey and included 1195 men and women. Metabolic syndrome was defined according to National Cholesterol Education Program Adult Treatment Panel III guidelines. There were 276 patients with metabolic syndrome and 872 controls. The Gly(16)-->Arg(16) (P < 0.005) and Gln(27)-->Glu(27) (P < 0.04) polymorphisms were associated with metabolic syndrome in men, but not in women. In multivariate analyses adjusting for age, physical activity, smoking habits, alcohol consumption, and body mass index, the odds ratio of metabolic syndrome was 1.83 (95% confidence interval, 1.10-3.05) and 2.43 (95% confidence interval, 1.19-4.95) in men bearing the Gly(16)/Arg(16) and Arg(16)/Arg(16) genotypes, respectively. Similarly, the odds ratios of metabolic syndrome were 0.99 (95% confidence interval, 0.50-1.93) and 1.67 (95% confidence interval, 0.84-3.33) in men bearing the Gln(27)/Glu(27) and Gln(27)/Gln(27) genotypes, respectively. Because both variants were in linkage disequilibrium, a haplotype analysis was performed. There was no evidence of any statistically significant association between beta(2)-adrenergic receptor haplotypes and metabolic syndrome. In conclusion, these data suggest that the Arg(16) and Gln(27) variants of the beta(2)-adrenergic receptor gene contribute to metabolic syndrome susceptibility in men.
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PMID:The Gly16-->Arg16 and Gln27-->Glu27 polymorphisms of beta2-adrenergic receptor are associated with metabolic syndrome in men. 1455 66

Hypertension is a major healthcare problem afflicting nearly 50 million individuals in the United States. Despite its strong causal association with cardiovascular disease complications including myocardial infarction, heart failure, and stroke, the majority of patients with hypertension do not achieve optimal blood pressure control. The prevalence of hypertension is expected to increase with the aging population, growing obesity epidemic, and rising incidence of metabolic syndrome. Endothelial dysfunction and reduced nitric oxide (NO) bioactivity represent prominent pathophysiological abnormalities associated with hypertensive cardiovascular disease. Individuals with hypertension exhibit blunted epicardial and resistance vascular dilation to endothelium-derived nitric oxide (EDNO) agonists in the peripheral and coronary circulation that likely contributes to mechanisms of altered vascular tone in hypertension. The amino acid L-arginine serves as the principal substrate for vascular NO production. Numerous studies, though not uniformly, demonstrate a beneficial effect of acute and chronic L-arginine supplementation on EDNO production and endothelial function, and L-arginine has been shown to reduce systemic blood pressure in some forms of experimental hypertension. This brief review discusses the potential role of L-arginine in hypertension, and reviews possible mechanisms of L-arginine action including modulation of EDNO production, alteration of asymmetrical dimethylarginine (ADMA):L-arginine balance, and possible improvement of insulin sensitivity. In view of the rising prevalence of hypertension, randomized human clinical studies investigating the potential therapeutic role of L-arginine may be warranted.
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PMID:L-arginine and hypertension. 1546 90

The endogenous nitric oxide-synthase inhibitor asymmetrical dimethyl-L-arginine (ADMA) is elevated in patients with increased risk for arteriosclerosis. Obesity is a risk factor for cardiovascular disease. We measured plasma ADMA concentrations in morbidly obese women before and after weight loss following gastroplastic surgery. ADMA and symmetrical dimethyl-L-arginine concentrations were analyzed by HPLC from 34 female patients (age 41 +/- 7 yr) with a body mass index (BMI) of 49 +/- 1 kg/m2 before and 14 months after vertical ring gastroplasty. Age-matched healthy women (BMI < 25 kg/m2; n = 24) were studied as controls. After gastroplastic surgery, BMI decreased to 34 +/- 1 kg/m2 in obese women (P < 0.00001), and ADMA concentrations were reduced from 1.06 +/- 0.06 micromol/liter at baseline to 0.81 +/- 0.04 micromol/liter after weight loss (P < 0.00001). Symmetrical dimethyl-L-arginine plasma levels were not affected. ADMA correlated with high-sensitivity C-reactive protein at baseline (r = 0.42; P < 0.05) and after weight loss (r = 0.56; P < 0.005). No association with blood pressure or plasma lipids could be observed. ADMA concentrations were lower in controls (0.68 +/- 0.04 micromol/liter; P < 0.05) compared with obese patients before or after weight reduction. The decrease of highly elevated ADMA concentrations in morbidly obese patients is paralleled by improvement of parameters associated with the metabolic syndrome after weight loss.
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PMID:Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women. 1557 89


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