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: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin action is approximately doubled following a meal. The mechanism of postprandial insulin sensitization is dependent on hepatic parasympathetic nerves regulated by the prandial status. The nerves provide a permissive signal to the liver that allows insulin to cause the release of a putative hepatic insulin sensitizing substance (HISS) that selectively stimulates glucose uptake into skeletal muscle but not liver or adipose tissue. The parasympathetic signal has several steps identified in the regulatory pathway; acetylcholine acts on muscarinic receptors leading to activation of nitric oxide synthase and generation of HISS. The meal-induced insulin (MIS) sensitization requires hepatic GSH, which decreases with fasting and several disease states. Interfering with the MIS process results in severe insulin resistance with the response to insulin being reduced by approximately 50% to levels seen in the fasted state. A wide range of conditions have been shown to be associated with insulin resistance attributed to lack of the MIS process including insulin resistance; in chronic liver disease produced by chemical damage or bile duct ligation, hepatic denervation, sucrose fed rats, aging, spontaneously hypertensive rats, fetal alcohol exposed adult offspring, spontaneously insulin resistant rats, animals with pharmacological blockade of hepatic muscarinic receptors, NO synthase, cyclooxygenase, hepatic cGMP, and hepatic GSH levels. Pharmaceutical reversal of insulin resistance has been shown in several models using a variety of approaches including mimicking or potentiating the parasympathetic signal using cholinergic agonists, NO donors, cholinesterase antagonists, phosphodiesterase antagonists, and replenishment of hepatic GSH levels. These compounds are being evaluated for therapeutic application by our international academic/industry collaborative team. The MIS process has now been demonstrated in mice, rats, guinea pigs, cats, dogs, and humans, and has been demonstrated by independent laboratories.
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PMID:Pharmaceutical reversal of insulin resistance. 1563 5

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

PC12 cells, a widely used model neuronal cell line, are usually cultured in serum-supplemented medium. This report describes a serum-free medium for the culture of PC12 cells. PC12 cells grown in the two media types had similar growth rates and released dopamine in response to high potassium-induced calcium elevation. However, the levels of dopamine and of dopamine release in cells cultured in the serum-free medium were less than 10% of that in cells cultured in serum-supplemented medium. Dopamine levels recovered within 10 days if cells were returned to serum-supplemented medium, but dopamine release could not be recovered. Nerve growth factor (NGF) induced similar responses in PC12 cells cultured in both media, including phosphorylation of extracellular signal-regulated protein kinases and neurite extension. Transferrin was necessary for survival of neurite-bearing PC12 cells subcultured in serum-free medium and insulin promoted the cells proliferation. Ten days culture with NGF produced a similar increase in neurofilament expression and acetylcholinesterase activity in both media. These results suggest that PC12 in the hormonally defined serum-free media are qualitatively the same as those cultured in serum-supplemented media, and therefore this new culture protocol should enable more precise studies of PC12 cells culture in the absence of confounding unknown factors.
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PMID:Serum-free culture conditions for serial subculture of undifferentiated PC12 cells. 1616 86

We reported that a leaf extract (GLEt) obtained from an anti-diabetic plant, Gymnema montanum, an endangered species endemic to India, has anti-peroxidative and antioxidant effects on diabetic brain tissue in rats. Here we examined the effect of the extract on the activity of reduced brain and retinal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in streptozotocin (STZ)-induced diabetic male Wistar rats. Diabetic rats received GLEt orally (200 mg/kg bwt/d) for 12 wk, and changes in blood glucose, plasma insulin, the lipid peroxidation marker thiobarbituric acid-reactive substance (TBARS), and AChE and BChE activity were measured. The results confirmed prior reports that hyperglycemia significantly enhances TBARS levels in brain and retinal tissue and decreases AChE and BChE activity. Treatment with GLEt significantly reversed the impairment in enzymatic activity in addition to reducing the level of TBARS, suggesting that GLEt protects against the adverse effect of lipid peroxidation on brain and retinal cholinesterases. We suggest that GLEt could be useful for preventing the cholinergic neural and retinal complications of hyperglycemia in diabetes.
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PMID:Modulation of impaired cholinesterase activity in experimental diabetes: effect of Gymnema montanum leaf extract. 1618 84

Serum cholinesterase activity was measured in diabetes, hypertensive and diabetic/hypertensive patients. The sample consisted of volunteer patients and was divided in a control group (n=26), type 2 diabetic group (n=16), hypertensive group (n=12) and type 2 diabetic/hypertensive group (n=26). In addition, blood glucose, cholesterol and triglyceride levels were determined. Serum cholinesterase activity in the control group was significantly lower in relation to the other groups (p<0.001). Blood glucose levels were elevated in type 2 diabetic and type 2 diabetic/hypertensive groups. In vitro studies showed increased cholinesterase activity in the presence of glucose 5-100mM or insulin 0.5-25 UI (p<0.001). Cholesterol and triglycerides were at normal levels only in the control group. Possibly, a relationship exists between the increase in serum cholinesterase and the vascular complications in the diabetic patients, potentially stimulated by the levels of glycemia and dyslipidemia. Although patients were receiving different medicines, the increase in enzyme activity was similar in all groups. This enzymatic profile suggests a possible interference of the diseases in the catalytic mechanism of the serum cholinesterase enzyme.
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PMID:Serum cholinesterase activity in diabetes and associated pathologies. 1623 31

1. The aim of the present study was to clarify the role of ginsenoside Rh2 as the active compound in Panax ginseng root for lowering plasma glucose in animals. 2. Plasma glucose was assessed using the glucose oxidase method. Changes in the levels of insulin and C-peptide in plasma were measured by ELISA using commercially available kits. 3. After intravenous injection into fasting Wistar rats for 60 min, ginsenoside Rh2 (0.1-1.0 mg/kg) decreased plasma glucose in a dose-dependent manner. In parallel with the decrease in plasma glucose, increases in plasma insulin levels, as well as plasma C-peptide, were observed in rats receiving the same treatment. These effects of Rh2 were reversed by atropine (0.1-1.0 mg/kg), but not affected by the ganglionic nicotinic antagonists pentolinium or hexamethonium (both at 7.5 mg/kg). 4. Disruption of synaptically available acetylcholine (ACh) using an inhibitor of choline uptake (hemicholinium-3; 1-10 microg/kg) or an inhibitor of vesicular ACh transport (vesamicol; 1.5-3.5 mg/kg) abolished the actions of Rh2. In addition, physostigmine (0.1-0.5 mg/kg), at a concentration sufficient to inhibit acetylcholinesterase, enhanced the actions of the ginsenoside Rh2. Thus, mediation of the effects of Rh2 to enhance insulin secretion by ACh released from nerve terminals can be considered. 5. Blockade of the increase in plasma insulin and the plasma glucose-lowering action of Rh2 by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP; 5-10 microg/kg) indicates the participation of muscarinic M(3) receptors. Increases in plasma C-peptide level induced by Rh2 were also sensitive to 4-DAMP. 6. The results of the present study suggest that ginsenoside Rh2 has the ability to increase insulin secretion as a result of the release of ACh from nerve terminals that then stimulates muscarinic M(3) receptors in pancreatic cells. This finding shows the mechanism for the plasma glucose-lowering action of ginsenoside Rh2, that is one of the major principles contained in P. ginseng root. Thus, ginsenoside Rh2 may be applied as an adjuvant for the management of diabetes.
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PMID:Increase of insulin secretion by ginsenoside Rh2 to lower plasma glucose in Wistar rats. 1644 95

Controversial data exists concerning the impact of immunosuppressive therapy on the development of post-transplantation diabetes mellitus (PTDM). Therefore, we investigated glucose metabolism in healthy donors and in recipients of living-donor liver transplants (LD-LTX, n=18) without pre-existing diabetes mellitus before, on day 10, month 6, and month 12 after intervention. The computer-assisted analysis of glucose, insulin, and C-peptide profiles obtained from frequently sampled intravenous glucose tolerance tests allows to achieve an integrated view of factors controlling glucose tolerance, i.e., insulin sensitivity (SI), first and second phase insulin secretion (phi1 and phi2). SI of donors declined by day 10 after operation (SI 2.65 +/- 0.41 vs. 4.90 +/- 0.50 10(-4) minute(-1) microU ml(-1), P < 0.01) but returned to values as before after 6 months. Phi1 did not change. Phi(2), however, significantly increased by day 10 (8.57 +/- 0.82 10(9) minute(-1) to 13.77 +/- 1.53 10(9) minute(-1), P < 0.01) but was in the same range as before after 6 months. In parallel to donors SI of recipients progressively increased after LD-LTX. Phi1 did not alter in recipients. Phi2 continuously decreased and was not different from donors by month 12. The extent of liver injury assessed by liver enzyme concentrations and liver function represented by cholinesterase activity, albumin, and INR were closely related with changes of SI in donors and recipients during the first year after intervention. In conclusion, the extent of liver damage plays a predominant role in regulating glucose tolerance. No impact of immunosuppressive therapy on SI, phi1 and phi2 was detected.
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PMID:Major influence of liver function itself but not of immunosuppression determines glucose tolerance after living-donor liver transplantation. 1649 77

The cascade of Alzheimer's disease (AD) neurodegeneration is associated with persistent oxidative stress, mitochondrial dysfunction, impaired energy metabolism, and activation of pro-death signaling pathways. More recently, studies with human postmortem brain tissue linked many of the characteristic molecular and pathological features of AD to reduced expression of the insulin and insulin-like growth factor (IGF) genes and their corresponding receptors. We now demonstrate using an in vivo model of intracerebral Streptozotocin (ic-STZ), that chemical depletion of insulin and IGF signaling mechanisms combined with oxidative injury is sufficient to cause AD-type neurodegeneration. The ic-STZ-injected rats did not have elevated blood glucose levels, and pancreatic architecture and insulin immunoreactivity were similar to control, yet their brains were reduced in size and exhibited neurodegeneration associated with cell loss, gliosis, and increased immunoreactivity for p53, active glycogen synthase kinase 3beta, phospho-tau, ubiquitin, and amyloid-beta. Real time quantitative RT-PCR studies demonstrated that the ic-STZ-treated brains had significantly reduced expression of genes corresponding to neurons, oligodendroglia, and choline acetyltransferase, and increased expression of genes encoding glial fibrillary acidic protein, microglia-specific proteins, acetylcholinesterase, tau, and amyloid precursor protein. These abnormalities were associated reduced expression of genes encoding insulin, IGF-II, insulin receptor, IGF-I receptor, and insulin receptor substrate-1, and reduced ligand binding to the insulin and IGF-II receptors. These results demonstrate that many of the characteristic features of AD-type neurodegeneration can be produced experimentally by selectively impairing insulin/IGF functions together with increasing oxidative stress, and support our hypothesis that AD represents a neuro-endocrine disorder associated with brain-specific perturbations in insulin and IGF signaling mechanisms, i.e. Type 3 diabetes.
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PMID:Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease. 1662 31

The plasma glucose lowering action of fruits of cornus (Cornus officinalis), the major active constituent of Die-Huang-Wan, has been documented to mediate acetylcholine (ACh) release, which in turn to stimulate muscarinic M(3) receptors resulting in the enhancement of insulin secretion in rats with functional pancreatic beta-cells. The present study was conducted to investigate the effect of oleanolic acid, one of the active principles of cornus fruit, on the release of insulin in rats. After an intraperitoneal injection into the fasting Wistar rats for 90 min, oleanolic acid decreased the plasma glucose in a dose-dependent manner in parallel to an increase of plasma levels of insulin as well as C-peptide. Moreover, disruption of synaptic ACh using an inhibitor of choline uptake, hemicholinium-3, or vesicular acetylcholine transport, vesamicol, abolished these actions of oleanolic acid. Also, physostigmine at concentration sufficient to inhibit acetylcholinesterase enhanced the actions of oleanolic acid. Both the plasma glucose lowering action and the raised plasma levels of insulin and C-peptide induced by oleanolic acid were also inhibited by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP), but not affected by the ganglionic nicotinic antagonist, pentolinium or hexamethonium. The results suggest that oleanolic acid has an ability to raise the release of ACh from nerve terminals, which in turn to stimulate muscarinic M(3) receptors in the pancreatic cells and augment the insulin release to result in plasma glucose lowering action. Thus, oleanolic acid is one of the active principles responsible for the increase of plasma insulin produced by cornus fruit in rats.
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PMID:Release of acetylcholine to raise insulin secretion in Wistar rats by oleanolic acid, one of the active principles contained in Cornus officinalis. 1675 6

The mandarin Hon-Chi is the red yeast rice fermented with Monascus pilous and Monascus purpureus. The present study is designed to screen the effect of Hon-Chi on plasma glucose and investigate the possible mechanisms. After oral administration into fasting Wistar rats for 90min, Hon-Chi decreased the plasma glucose in a dose-dependent manner. In parallel to the reduction of plasma glucose, an increase of plasma level of insulin or C-peptide was also observed in rats receiving same treatment. Moreover, disruption of synaptic available acetylcholine (ACh) using an inhibitor of choline uptake, hemicholinium-3, or vesicular acetylcholine transport, vesamicol, abolished these actions of Hon-Chi. Also, physostigmine at concentration sufficient to inhibit acetylcholinesterase enhanced the actions of Hon-Chi. Mediation of ACh release from the nerve terminals to enhance insulin secretion by Hon-Chi can thus be considered. Both the plasma glucose lowering action and the raised plasma levels of insulin and C-peptide induced by Hon-Chi were also inhibited by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP), but not affected by the ganglionic nicotinic antagonist, pentolinium or hexamethonium, indicating the mediation of muscarinic M(3) receptors. The results suggest that Hon-Chi has an ability to raise the release of ACh from nerve terminals, which in turn to stimulate muscarinic M(3) receptors in pancreatic cells and augment the insulin release to result in plasma glucose lowering action. Thus, Hon-Chi seems suitable to employ as the health food for increase of insulin secretion in the prevention of type-2 diabetes.
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PMID:Release of acetylcholine by Hon-Chi to raise insulin secretion in Wistar rats. 1676 3


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