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)

There is ample evidence from many epidemiological studies that lower urinary tract symptoms (LUTS) and sexual dysfunction are strongly linked, independently of age and comorbidities such as hypertension, diabetes, dyslipidaemia and coronary heart disease. However, a causal link between both conditions is not yet established. Four pathophysiological mechanisms currently support the relationship between LUTS and erectile dysfunction (ED): (i) The nitric oxide synthase (NOS)/NO theory; there is a reduction in NOS-containing nerves in the prostate and bladder/urethra in patients with bladder outlet obstruction (BOO), and that lack of NO or loss of protein kinase G causes ED; (ii) The autonomic hyperactivity and metabolic syndrome hypothesis: benign prostatic hyperplasia (BPH) may be part of the metabolic syndrome, which includes cardiovascular diseases (e.g. hypertension, ischaemic heart disease) and diabetes mellitus, known risk factors for ED. Hypertension, obesity, and hyperinsulinaemia have all been claimed to be associated with an increased sympathetic activity. Increased sympathetic activity is involved in LUTS/BPH and may have a role in ED/sexual dysfunction, with noradrenaline and alpha1-adrenoceptors representing a common link; (iii) the Rho-kinase activation/endothelin pathway; there can be increased Rho-kinase activity, and consequently calcium sensitivity of the contractile machinery, in prostate smooth muscle in BPH, the detrusor in BOO, corpora cavernosa in ED, and in the resistance vessels in hypertension. The actions of several factors beside noradrenaline (e.g. endothelin-1, angiotensin II), possibly involved in the increased smooth muscle activity found in both LUTS/BPH and sexual dysfunction, are dependent on Rho-kinase activity. Thus increased Rho-kinase activity might represent a common link between LUTS and sexual dysfunction; (iv) Pelvic atherosclerosis; animal models mimicking pelvic ischaemia and hypercholesterolaemia show similar smooth muscle alterations of the detrusor and corpora. Pelvic ischaemia may induce the biological modifications described above and may thus represent as well a common link between LUTS and sexual dysfunction. Studies treating one condition (e.g. ED) and measuring the impact on the other (e.g. LUTS) should further contribute to support this common link.
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PMID:Lower urinary tract symptoms and sexual dysfunction: epidemiology and pathophysiology. 1650 50

The insulin resistance syndrome, which presents among its many facets obesity and type 2 diabetes mellitus, is a major risk factor for cardiovascular events. Thus, therapeutic guidelines recommend multifactorial treatment programs including, especially in the presence of type 2 diabetes, antiplatelet drugs. Few data, however, are available about the protective effect of antiplatelet therapy in both obese and type 2 diabetic patients. Furthermore, some reports showed a decreased sensitivity to the platelet antiaggregating effect of acetylsalicylic acid in diabetic patients. In the first part of this review, we focused our attention to alterations of platelets from insulin resistant subjects with or without type 2 diabetes, underlining that platelet hyperactivation is explained, at least in part, by: i) a reduced sensitivity to agents exerting an inhibitory modulation of platelet responses, ii) an altered intracellular milieu with elevated cytosolic Ca2+, iii) an enhanced thromboxane A2 synthesis, and iv) an increased number and/or function of GPIIb/IIIa complexes on platelet membranes. Furthermore, oxidative stress, which increases isoprostane production from arachidonic acid, may be involved in platelet hyperactivation, since isoprostanes activate platelets by interplaying with thromboxane receptors. These defects explain why antiplatelet therapy for both chronic atherosclerotic vascular disease and acute coronary syndromes should be specifically tailored in obese, insulin resistant subjects, especially in the presence of type 2 diabetes mellitus. Thus, in the second part of this review we carried out a critical overview of the clinical trials in subjects with metabolic syndrome and type 2 diabetes mellitus with or without macroangiopathy.
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PMID:Pathophysiology of platelet resistance to anti-aggregating agents in insulin resistance and type 2 diabetes: implications for anti-aggregating therapy. 1661 Oct 47

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 purpose of this review is to summarize experimental findings showing that magnesium modulates cellular events involved in inflammation. Experimental magnesium deficiency in the rat induces after a few days a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, release of inflammatory cytokines and acute phase proteins, excessive production of free radicals. Increase in extracellular magnesium concentration, decreases inflammatory response while reduction in the extracellular magnesium results in cell activation. Because magnesium acts as a natural calcium antagonist, the molecular basis for inflammatory response is probably the result of modulation of intracellular calcium concentration. The priming of phagocytic cells, the opening calcium channel and activation of N-methyl-d-aspartate (NMDA) receptors, the activation of nuclear factor-kappa B (NFkappaB) have been considered as potential mechanisms. Moreover, magnesium deficiency induces a systemic stress response by activation of neuro endocrinological pathways. As nervous and immune systems interact bidirectionally, the roles of neuromediators have also been considered. Magnesium deficiency contributes to an exaggerated response to immune stress and oxidative stress is the consequence of the inflammatory response. Inflammation contributes to the pro-atherogenic changes in lipoprotein metabolism, endothelial dysfunction, thrombosis, hypertension and explains the aggravating effect of magnesium deficiency on the development of metabolic syndrome. Further studies are still needed to assess more accurately the role of magnesium in immune response in humans, but these experimental findings in animal models suggest that inflammation is the missing link to explain the role of magnesium in many pathological conditions.
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PMID:Magnesium and the inflammatory response: potential physiopathological implications. 1671 75

An increased prevalence of nephrolithiasis has been reported in patients with diabetes. Because insulin resistance, characteristic of the metabolic syndrome and type 2 diabetes, results in lower urine pH through impaired kidney ammoniagenesis and because a low urine pH is the main factor of uric acid (UA) stone formation, it was hypothesized that type 2 diabetes should favor the formation of UA stones. Therefore, the distribution of the main stone components was analyzed in a series of 2464 calculi from 272 (11%) patients with type 2 diabetes and 2192 without type 2 diabetes. The proportion of UA stones was 35.7% in patients with type 2 diabetes and 11.3% in patients without type 2 diabetes (P < 0.0001). Reciprocally, the proportion of patients with type 2 diabetes was significantly higher among UA than among calcium stone formers (27.8 versus 6.9%; P < 0.0001). Stepwise regression analysis identified type 2 diabetes as the strongest factor that was independently associated with the risk for UA stones (odds ratio 6.9; 95% confidence interval 5.5 to 8.8). The proper influence of type 2 diabetes was the most apparent in women and in patients in the lowest age and body mass index classes. In conclusion, in view of the strong association between type 2 diabetes and UA stone formation, it is proposed that UA nephrolithiasis may be added to the conditions that potentially are associated with insulin resistance. Accordingly, it is suggested that patients with UA stones, especially if overweight, should be screened for the presence of type 2 diabetes or components of the metabolic syndrome.
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PMID:Type 2 diabetes increases the risk for uric acid stones. 1677 30

Impaired insulin-mediated vasodilation has been implicated in hypertension that is associated with the metabolic syndrome. The aim of this study was to determine whether an abnormality in membrane fatty acid composition was related to a weakening of insulin's inhibitory effect on agonist-stimulated intracellular free calcium elevation. Mild to moderate hypertensive patients (n = 27) and normotensive controls (n = 11) were studied. Hypertensive patients were divided into normoinsulinemic patients (n = 14) and hyperinsulinemic patients (n = 13) according to the area under the curve of plasma insulin concentrations during a 75-g oral glucose tolerance test. Nonstimulated and arginine-vasopressin (AVP) (1 micromol/l)-stimulated intraplatelet free calcium concentrations (p[Ca(2+)](i)) were measured with or without insulin (100 microU/ml) preincubation. Platelet membrane fatty acid composition, intraerythrocyte sodium content, and the ouabain-sensitive sodium efflux rate constant (K (os)) of erythrocytes were also determined. Insulin preincubation reduced AVP-stimulated p[Ca(2+)](i) elevation in both normotensive controls and hypertensive patients. The inhibitory effect of insulin on AVP-stimulated elevation of p[Ca(2+)](i) (%Inhibition) was significantly (P < 0.05) blunted in hyperinsulinemic hypertensive patients (9.7% +/- 2.4%) as compared to normoinsulinemic hypertensive patients (17.4% +/- 2.7%) and normotensive controls (16.9% +/- 1.7%). In hypertensive patients, the %Inhibition was correlated negatively with saturated fatty acids (SFA) (r = -0.51, P < 0.05) and systolic blood pressure (r = -0.44, P < 0.05), and correlated positively with membrane polyunsaturated fatty acids (PUFA) (r = 0.53, P < 0.01) and K (os) (r = 0.53, P < 0.005). Multiple regression analysis showed that SFA, PUFA, and K (os) were the significant variables for %Inhibition. These findings indicate that an increase in SFA and a decrease in PUFA may cause insulin insensitivity in cellular calcium and sodium handling in hypertension with hyperinsulinemia.
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PMID:Inhibitory effect of insulin on vasopressin-induced intracellular calcium response is blunted in hyperinsulinemic hypertensive patients: role of membrane fatty acid composition. 1686 95

The number of obesity and diabetes mellitus in the world has been rapidly increasing in population. Current lifestyle initiates obesity, especially visceral fat accumulation, and leads to the onset of metabolic syndrome, such as cardiovascular events, hyperlipidemia and diabetes mellitus, based on insulin resistance. Several studies of adipocyte function have revealed that adipose tissue is not merely an energy-storing organ but it secretes a variety of biologically active molecules, conceptualized as "adipocytokines", including tumor necrosis factor-alpha, estrogen, leptin and adiponectin and that abnormal secretion of these adipocytokines causes metabolic syndrome. Adipocytes exist not only in the visceral and subcutaneous tissue but also in the bone marrow. Therefore, it is important to know their effects not only on glucose and lipid metabolism but also on bone metabolism. This report aims to review some of the effects of visceral fat accumulation by diabetes mellitus on bone metabolism.
Clin Calcium 2006 Aug
PMID:[The effects of visceral fat accumulation by diabetes mellitus on bone metabolism]. 1688 42

The calpain family is a group of cysteine proteases unique in their dependency on calcium to attain functionally active forms. Calpains are involved in a wide range of cellular calcium-regulated functions, including signal transduction, cell proliferation and differentiation, and apoptosis. Moreover, altered calpain activity has been observed in several human diseases. Specific calpain inhibitors hold promise for the treatment of neuromuscular and neurodegenerative diseases in which calpains have been shown to be upregulated (e.g. Parkinson's disease and Duchenne muscular dystrophy). Conversely, calpain activators could be a useful approach for those diseases where reduced calpain activity has been observed, such as type 2 diabetes or metabolic syndrome.
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PMID:The therapeutic potential of the calpain family: new aspects. 1699 42

Gallstone disease is common: >700,000 cholecystectomies and costs of approximately 6.5 billion dollars annually in the U.S. The burden of disease is epidemic in American Indians (60-70%); a corresponding decrease occurs in Hispanics of mixed Indian origin. Ten to fifteen per cent of white adults in developed countries harbour gallstones. Frequency is further reduced in Black Americans, East Asia and sub-Saharan Africa. In developed countries, cholesterol gallstones predominate; 15% are black pigment. East Asians develop brown pigment stones in bile ducts, associated with biliary infection or parasites, or in intrahepatic ducts (hepatolithiasis). Certain risk factors for gallstones are immutable: female gender, increasing age and ethnicity/family (genetic traits). Others are modifiable: obesity, the metabolic syndrome, rapid weight loss, certain diseases (cirrhosis, Crohn's disease) and gallbladder stasis (from spinal cord injury or drugs like somatostatin). The only established dietary risk is a high caloric intake. Protective factors include diets containing fibre, vegetable protein, nuts, calcium, vitamin C, coffee and alcohol, plus physical activity.
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PMID:Gallstone disease: Epidemiology of gallbladder stone disease. 1712 83

Epidemiological data suggest an association between kidney stones and some features of metabolic syndrome such as an overweight condition, arterial hypertension or glucose intolerance. However, mechanisms remain to be elucidated. This study aimed to evaluate insulin resistance, as assessed by homeostasis model assessment (HOMA-IR), and urine composition analysis in patients affected by calcium nephrolithiasis. A cohort of 61 (38 male, 29-57 years of age) non-diabetic calcium stone formers was studied. Data about body mass index, arterial blood pressure, serum biochemistry including parathyroid hormone and calcitriol were recorded in all the patients; fasting glucose and insulin were determined to calculate HOMA-IR value and accordingly the patients were grouped into tertiles. Urine pH and urinary excretion of calcium, citrate, phosphate, oxalate, uric acid, urea and creatinine were measured on 24h urine samples. Patients of the highest HOMA-IR tertile showed lower urine citrate levels than patients of the lowest HOMA-IR tertile (475+/-243 vs. 630+/-187 mg/24h, p<0.05), whereas no difference was detected as far as urinary oxalate, calcium, uric acid, phosphate, and urine pH and urine volume output were concerned. HOMA-IR values were positively related to uric acid serum levels (r=0.31, p<0.05) and negatively to urinary citrate excretion (r=-0.26, p<0.05). Hypocitraturic patients showed higher levels of HOMA-IR than normocitraturic ones (3.03+/-0.92 vs. 2.25+/-1.19, p<0.05). This study shows that a higher level of insulin resistance is associated with lower urinary citrate excretion, and that hypocitraturic patients show a greater insulin resistance than normocitraturic calcium stone formers. This may be related to changes in citrate, Na(+)-K(+) and H(+) renal tubule transports, which have been described in insulin resistance. In conclusion, insulin resistance may contribute to an increased risk of calcium stone formation by lowering urinary citrate excretion. This finding suggests the need for a careful metabolic assessment in patients known to form calcium stones in order to ensure stone recurrence prevention and cardiovascular protection.
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PMID:Insulin resistance and low urinary citrate excretion in calcium stone formers. 1718 67


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