Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011860 (type 2 diabetes)
57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The activity of serum butyrylcholinesterase ('pseudocholinesterase', EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51 patients with type 2 diabetes mellitus and 101 healthy control subjects. 2. Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 +/- 3.35 units/ml) and type 2 (7.22 +/- 1.95 units/ml) diabetes compared with the control subjects (4.23 +/- 1.89 units/ml) (P < 0.001). 3. In the patients with type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated with log serum fasting triacylglycerol concentration (r = 0.41 and r = 0.43, respectively, P < 0.001). In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity (r = -0.51, P < 0.001). 4. Serum butyrylcholinesterase activity was unrelated to age, gender, serum gamma-glutamyltranspeptidase activity, body mass index, or treatment for diabetes in both the diabetic populations. 5. In 37 non-diabetic patients with butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus.
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PMID:Relationship between serum butyrylcholinesterase activity, hypertriglyceridaemia and insulin sensitivity in diabetes mellitus. 814 99

Hypertriglyceridaemia is a risk factor for cardiovascular disease in patients suffering from Type II diabetes mellitus, and is due to enhanced synthesis and/or impaired clearance of triacylglycerol-rich lipoproteins. In the present study we investigated whether pseudocholinesterase (PChE) activity could serve as a marker for the rate of triacylglycerol synthesis in these patients. Patients were stratified according to their apolipoprotein E (apoE) phenotype, i.e. E3E2, E3E3 or E3E4. In study I, the relationship between PChE activity and serum triacylglycerols was investigated in 224 insulin-treated patients with Type II diabetes. In study II, which had a cross-over design, PChE activity was measured in 45 dyslipidaemic, insulin-treated patients with Type II diabetes that were treated with bezafibrate or pravastatin. In study I, PChE activity was correlated positively with serum triacylglycerol concentrations, but did not differ significantly between apoE phenotypes. The strongest relationship was found in the E3E4 group (r=0.50; P=0.001), the phenotype for which hypertriglyceridaemia is expected to be the result of increased triacylglycerol synthesis. In a stepwise multiple regression analysis, serum triacylglycerol concentrations were found to be the strongest predictor of PChE activity in the E3E4 group. In study II, PChE activity decreased as a result of bezafibrate treatment in all three apoE groups. The decrease in PChE activity with bezafibrate treatment paralleled the decrease in serum triacylglycerol concentrations in the apoE subgroups. Pravastatin treatment did not significantly affect PChE activity. Thus the present study suggests an association between PChE activity and the rate of triacylglycerol synthesis. Measurement of PChE activity may therefore be a useful tool in the choice of drug for treatment of hypertriglyceridaemia in patients with Type II diabetes.
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PMID:Is pseudocholinesterase activity related to markers of triacylglycerol synthesis in Type II diabetes mellitus? 1141 Jan 11

The central role of the intracellular enzyme hormone-sensitive lipase (HSL) in regulating fatty acid metabolism makes it an interesting pharmacological target for the treatment of insulin resistant and dyslipidemic disorders where a decrease in delivery of fatty acids to the circulation is desirable, e.g., in individuals with type 2 diabetes, metabolic syndrome, or impaired glucose tolerance. On the basis of a lead structure from high throughput screening, we have identified a very potent type of carbamoyl-triazole inhibitors of HSL. As part of the lead optimization program, four new classes of carbamoyl-triazoles were synthesized and tested with respect to potency, efficacy and selectivity. Methyl-phenyl-carbamoyl-triazoles were identified as potent and efficacious HSL inhibitors. These compounds do not inhibit other hydrolases such as hepatic lipase, lipoprotein lipase, pancreatic lipase, and butyrylcholine esterase. However, the inhibitors 4b and 4g with IC(50) values for HSL of 0.17 and 0.25 microM, respectively, were the only inhibitors selective against acetylcholine esterase. A reversible pseudosubstrate inhibition mechanism is proposed for this class of inhibitors.
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PMID:Synthesis and structure-activity relationship for a novel class of potent and selective carbamoyl-triazole based inhibitors of hormone sensitive lipase. 1471 11

When compared with values recorded in 14 control subjects, the 15 overweight patients with type 2 diabetes displayed significantly increased activities of serum alanineaminotransferase (172% of mean values in controls), gamma-glutamyltransferase (253%) and cholinesterase (139%). A much wider dispersion of individual values for the two firstly mentioned enzymes was however noted so that their correlation with serum triglycerides levels were weaker (r = 0.373; p < 0.05 and r = 0.451; p < 0.05 respectively) than the same correlation obtained for serum cholinesterase (r = 0.760; p < 0.001). In two other studies including 28 controls and 30 diabetic patients serum cholinesterase was found to be significantly correlated with serum levels of insulin (r = 0.622; p < 0.001), C-peptide (r = 0.652; p < 0.001) and free fatty acid (r = 0.821; p < 0.001). Circumstantial evidence is provided that insulin resistance and an increased flux of free fatty acids from adipose tissue to the liver would stimulate the hepatic synthesis of serum cholinesterase.
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PMID:Serum cholinesterase activity correlates with serum insulin, C-peptide and free fatty acids levels in patients with type 2 diabetes. 1552 39

Thirty-three patients with type 2 diabetes mellitus (16 men, 17 women) were divided into 3 groups based on urinary excretion of albumin (U-Alb)--group A: U-Alb < 30 mg/d; group B: 30 mg/d < or = U-Alb < or = 300 mg/d; and group C: 300 mg/d < U-Alb. Serum creatinine levels were lower than 2.0 mg/dL in all the subjects. There was no difference in age, sex, therapy, body weight, body mass index (BMI), lean body mass (LBM), or hemoglobin A(1c) (HbA(1c)) levels among the 3 groups. Resting metabolic rate (RMR) (kJ/h/m(2)) and adjusted RMR for lean body mass (kJ/h/m(2)) were significantly increased in group C compared with groups A and B. Hb concentrations, serum albumin levels, and creatinine clearance were much lower in group C than in groups A and B (P < .001). There were no difference in serum urea nitrogen, total cholesterol, cholinesterase and free thyroxine, or plasma insulin-like growth factor I (IGF-I) levels among the 3 groups. Linear regression analysis revealed an inverse correlation between RMR and serum albumin levels, correlation between RMR and U-Alb, and inverse correlation between RMR and Hb concentrations, respectively, in these patients. In conclusion, RMR in diabetic patients correlated directly with U-Alb and inversely with serum albumin and Hb concentration. These findings suggest that RMR is related with urinary albumin loss and anemia in patients with type 2 diabetes mellitus accompanied by diabetic nephropathy.
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PMID:Increased resting metabolic rate in patients with type 2 diabetes mellitus accompanied by advanced diabetic nephropathy. 1553 91

We measured liver fat content by 3-Tesla magnetic resonance spectroscopy (MRS) in 34 non- to mild obese Japanese subjects with type 2 diabetes, who were not complicated with any liver diseases including clinical fatty liver (liver/spleen ratio of computed tomography [CT] < 0.9) and were not being treated with oral hypoglycemic agents, insulin, or lipid-lowering agents, and analyzed the relationship between liver fat content and body composition and plasma metabolite. The liver fat content is significantly correlated with variables relating to obesity (body mass index [BMI], body weight, fat mass, waist to hip ratio, visceral fat area, subcutaneous fat area, and serum triglyceride), insulin resistance (fasting plasma insulin and homeostasis model assessment of insulin resistance [HOMA-IR]), adipocytokines (serum plasminogen activator inhibitor-1 [PAI-1] and leptin), and serum cholinesterase, but not CT liver/spleen ratio, which is correlated only with fasting plasma glucose, BMI, and HOMA-IR. Multiple regression analysis revealed that the liver fat content is independently associated with serum PAI-1 level (p < 0.001) and BMI (p < 0.05), but not visceral fat area. MRS is a more sensitive method for quantifying liver fat content than CT in type 2 diabetic subjects with non- to mild obesity and without clinical fatty liver.
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PMID:Liver fat content measured by magnetic resonance spectroscopy at 3.0 tesla independently correlates with plasminogen activator inhibitor-1 and body mass index in type 2 diabetic subjects. 1580 72

Alzheimer's disease and type 2 diabetes mellitus tend to occur together. We sought to identify protein(s) common to both conditions that could suggest a possible unifying pathogenic role. Using human neuronal butyrylcholinesterase (AAH08396.1) as the reference protein we used BLAST Tool for protein to protein comparison in humans. We found three groups of sequences among a series of 12, with an E-value between 0-12, common to both Alzheimer's disease and diabetes: butyrylcholinesterase precursor K allele (NP_000046.1), acetylcholinesterase isoform E4-E6 precursor (NP_000656.1), and apoptosis-related acetylcholinesterase (1B41|A). Butyrylcholinesterase and acetylcholinesterase related proteins were found common to both Alzheimer's disease and diabetes; they may play an etiological role via influencing insulin resistance and lipid metabolism.
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PMID:Alzheimer's disease and type 2 diabetes mellitus: the cholinesterase connection? 1709 57

Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and lipid peroxides are elevated and concentrations of endothelial nitric oxide (eNO) decreased in type 2 diabetes mellitus and Alzheimer's disease. This suggests that both these diseases are low-grade systemic inflammatory conditions and are closely associated with each other. Recent studies revealed that plasma and tissue concentrations of enzymes butyrylcholinesterase and acetylcholinesterase are elevated in type 2 diabetes and Alzheimer's disease. Acetylcholine has anti-inflammatory actions. Hence, elevated butyrylcholinesterase and acetylcholinesterase concentrations will lead to a decrease in the levels of acetylcholine that could trigger the onset of low-grade systemic inflammation seen in type 2 diabetes and Alzheimer's disease. In view of this, we propose that butyrylcholinesterase and acetylcholinesterase will not only serve as therapeutic targets but also may serve as markers to predict the development of type 2 diabetes mellitus and Alzheimer's disease.
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PMID:Elevated butyrylcholinesterase and acetylcholinesterase may predict the development of type 2 diabetes mellitus and Alzheimer's disease. 1755 29

The conflicting results of several studies suggest that there is an association between the butyrylcholinesterase-K variant (BCHE-K, G1615A/Ala539Thr) and the risk of developing coronary artery disease (CAD) in diabetes and non-diabetic subjects. The objective of this study was to determine whether the presence of the BCHE-K variant exacerbates the risk of CAD in patients from western Iran with and without type 2 diabetes mellitus (T2DM). This case-control study comprised 464 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: CAD+T2DM+ (CAD/T2DM), CAD+DM(-) (CAD/ND), CAD(-)DM+ (T2DM/NCAD) and CAD(-)DM(-)(control). The BCHE-K variant was detected by PCR-RFLP. The BCHE-K allele frequency in CAD patients with and without T2DM [total CAD (TCAD)] and separately for each group (CAD/T2DM and CAD/ND) was significantly higher than in the control group (21.1 % versus 13.3 % (p = 0.001), 22.4 % versus 13.3 % (p = 0.001) and 19.7 % versus 13.3 % (p = 0.015), respectively). The odds ratios (ORs) for the BCHE-K heterozygous and homozygous variants in TCAD subjects were 1.65 (95 % CI 1.17-2.3; p = 0.004) and 4.3 (1.05-19.4; p = 0.048); for CAD/T2DM individuals 1.76 (1.2-2.6; p = 0.004) and 4.73 (0.96-23.3; p = 0.052); and for CAD/ND patients 1.53 (1.05-2.3; p = 0.029) and 3.88 (0.8-19.7; p = 0.7), respectively. The OR of the BCHE-K allele was found to be 1.74 (1.1-2.4; p = 0.001) in TCAD subjects, 1.87 (1.12-1.48; p = 0.001) in the CAD/T2DM group and 1.59 (1.04-1.4; p = 0.016) in CAD/ND subjects. These data suggest that the BCHE-K allele increases the risk of CAD in the population (with and without DM) in western parts of Iran, and its presence intensifies the risk of CAD in T2DM. The fact that the BCHE-K allele, even in the heterozygous form, exacerbates the risk of CAD in this population, suggests that a specific therapeutic intervention should be considered for this particular group of patients.
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PMID:Butyrylcholinesterase K variants increase the risk of coronary artery disease in the population of western Iran. 1785 36

Plasma levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and lipid peroxides are high whereas those of endothelial nitric oxide are low in insulin resistance, obesity, type 2 diabetes mellitus, hypertension, hyperlipidemias, metabolic syndrome X, and Alzheimer's disease suggesting that these diseases are characterized by low-grade systemic inflammation. Recent studies showed that the plasma and tissue activities of enzymes butyrylcholinesterase and acetylcholinesterase are elevated in patients with Alzheimer's disease, and diabetes mellitus, hypertension, insulin resistance, and hyperlipidemia. As a result of this increase in the activities of enzymes acetylcholinesterase and butyrylcholinesterase, the plasma and tissue levels of acetylcholine (ACh) will be low. The "cholinergic anti-inflammatory pathway" mediated by acetylcholine acts by inhibiting the production of tumor necrosis factor, interleukin-1, macrophage migration inhibitory factor, and high mobility group box-1 and suppresses the activation of nuclear factor-kappa B expression. ACh is a neurotransmitter and regulates the levels and activities of serotonin, dopamine and other neuropeptides and thus, modulates both immune response and neurotransmission. Hence, both acetylcholinesterase and butyrylcholinesterase by inactivating acetylcholine may enhance inflammation. This suggests that increased plasma and tissue activities of acetylcholinesterase and butyrylcholinesterase seen in various clinical conditions could serve as a marker of low-grade systemic inflammation.
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PMID:Acetylcholinesterase and butyrylcholinesterase as possible markers of low-grade systemic inflammation. 1804 45


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