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:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The receptors for insulin and insulin-like growth factor I (IGF-I) are closely related molecules, with an extracellular binding domain and an intracellular tyrosine kinase domain. The interaction of insulin and IGF-I with their respective receptors activates the receptor kinase domain, leading to the biological actions of the hormones. Since insulin generally regulates metabolic events and IGF-I generally regulates growth events, it is believed that structural differences in the tyrosine kinase domains of the two respective receptors may elicit different biological responses via different transmembrane signaling mechanisms. We studied the regulation of glycogen metabolism and amino acid uptake in human cultured HEP-G2 hepatoma cells, which have distinct receptors for both insulin and IGF-I. The receptor specificity of these responses was probed with specific monoclonal antibodies to both the insulin and IGF-I receptors. Stimulation of both [3H]glucose incorporation into glycogen and alpha-[3H]aminoisobutyric acid uptake by insulin was half-maximal at concentrations of 1-5 nmol/L. These effects were blocked by the insulin receptor monoclonal antibody MA-10, but not by the IGF-I receptor antibody alpha IR-3. Stimulation of both functions by IGF-I was half-maximal at concentrations of 1-5 nmol/L, and these effects were inhibited by alpha IR-3, but not by MA-10. These studies indicate that in HEP-G2 cells both insulin and IGF-I, via their own receptors, stimulate the same biological responses.
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PMID:Insulin and insulin-like growth factor I regulate the same biological functions in HEP-G2 cells via their own specific receptors. 283 99

A comparative study of the metabolic effects of two combined oral contraceptive preparations was undertaken in seven WHO Collaborating Centres for Research in Human Reproduction. A total of 847 subjects were randomly allocated to one of two pill groups - norethisterone lmg/ethinyl estradiol 35 micrograms (NET/EE) or levonorgestrel 150 micrograms/ethinyl estradiol 30 micrograms (LNG/EE). An additional 195 women using an IUD served as a comparison group. Blood samples were taken on admission, and at 3 and 12 months thereafter. Both pills induced changes in fasting and 2-hour glucose, triglycerides, total cholesterol, HDL-cholesterol, bilirubin, alkaline phosphatase, albumin, and total protein, but not aspartate aminotransferase. The most dramatic and probably most clinically important changes were an increase in triglycerides and a decrease in HDL-cholesterol. The NET/EE preparation appeared to induce a greater increase in triglycerides, but no significant difference was found between the two pill preparations with respect to HDL-cholesterol changes.
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PMID:A randomized double-blind study of the effects of two low-dose combined oral contraceptives on biochemical aspects. Report from a seven-centred study. WHO Special Programme of Research, Development and Research Training in Human Reproduction. Task force on Oral Contraceptives. 286 58

Energy reserves (TAN) and anaerobic substrates (glucose, glycogen) are lower in renal than in myocardial tissue. Euro-Collins-solution contains nearly 200 mmol/l glucose, while the HTK-solution of Bretschneider contains none. Therefore the influence of glucose on kidney lactate production, on energy reserves (TAN), intrarenal pH and on morphology during the protection of ischemic kidneys was analysed using either Euro-Collins-solution, or modified "Euro-Collins-solution", containing mannitol instead of glucose, or HTK-solution with and without the addition of 5, 10 and 20 mmol/l glucose. Glucose content changed during kidney perfusion with Euro-Collins-solution from about 60 to 800 mumol/gdw. While intrarenal pH decreased from 7.1 to 5.1 in Euro-Collins-kidneys during 420 min of ischemia at 25 degrees C, pH decreased to 6.7 with the modified, mannitol containing "Euro-Collins-solution". In HTK-protected kidneys intrarenal pH decreased with increasing glucose addition to the solution. Although Total Adenine Nucleotides are highest at the end of ischemia with Euro-Collins-solution, structural protection after the same ischemic stress was best in HTK-protected kidneys without glucose addition. We conclude that glucose stimulated lactate production, reduced interstitial pH in the kidney even in combination with a highly buffered solution and that it might cause greater membrane permeability leading to a structural deterioration. Mannitol seemed more appropriate than glucose in this respect, although other substances, which provide energy substrate and prevent structural damage, may exist.
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PMID:Effects of glucose in protected ischemic kidneys. 311 45

We checked the effect of a 4 hourly computer controlled submaximal glucose utilization (CCSGU) of 12.01 +/- 1.19 mg/kg min under normoglycaemic conditions and of a simultaneous diminishing of myocardial NEFA supply on trigger mechanism of ventricular fibrillation during acute strophantin intoxication (4 micrograms/kg min) in 17 mongrel dogs. Dogs treated with CCSGU (protective group, n = 8) showed a nearly 30% (p less than 0.01) major survival time (47.6 +/- 3.6 min) before ventricular fibrillation occurred in comparison to a control group (33.1 +/- 3.7 min, n = 9). CCSGU induced a 90% higher left ventricular hydraulic work (5.18 +/- 0.57 Nm/g heart weight) during strophantin infusion compared to controls (2.75 +/- 0.47). No significant myocardial NEFA extraction was evident in the protective group. During CCSGU myocardial oxygen extraction was on a lower level in rest (15.8 +/- 1.0%, p less than 0.01) as well as during strophantin infusion (11.3 +/- 2.6%, p less than 0.01) compared to controls. In dogs treated with CCSGU nearly equal myocardial levels of HEP and lactate were found compared to controls in spite of a major survival time and higher left ventricular hydraulic work. A higher myocardial glycogen content was observed in the protective group (45.1 +/- 6.7 mumol/g w.w.) in comparison to controls (28.1 +/- 2.9, p less than 0.05). Our results prove that CCSGU using the device system GLUCON induces a shift in substrate utilization from NEFA to glucose, decreases myocardial oxygen extraction, increases myocardial glycogen content, enlarges heart work and protects against strophantin induced ventricular fibrillation.
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PMID:Effects of computer controlled submaximal glucose utilization on myocardial energy potential and on survival time during acute strophantin intoxication in dogs. 332 46

The C-terminal eight-amino acid derivative of CCK, sulfated on the tyrosine residue (CCK8S), stimulated a dose-dependent biphasic pattern of insulin secretion from isolated perifused islets in the presence of 7 mM glucose. It was without any effect if glucose were absent from the medium or maintained at 4 mM. The response to CCK8S was readily reversible and dependent on the presence of extracellular calcium. While CCK8S did not increase glucose usage rates above those noted with 7 mM glucose alone, inclusion of the metabolic inhibitor 2-deoxyglucose lowered glucose usage rates to values obtained with 3-5 mM glucose and abolished the influence of CCK8S on insulin output. Removal of the metabolic inhibitor restored the secretory response. N-Acetylglucosamine (15 mM) or glyceraldehyde (2.5 mM) substituted for glucose and permitted CCK8S to evoke secretion. The nonsulfated eight-amino acid derivative of CCK, CCK8, provoked insulin secretion in the presence of 7 mM glucose, but only at 10-100 times greater levels than CCK8S. CCK4 (1 microM) did not influence insulin output in the presence of 7 mM glucose. On an equimolar basis, CCK8S was significantly more effective than gastric inhibiting polypeptide in augmenting insulin output. The results support a role for CCK8S in the regulation of insulin levels in vivo.
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PMID:Influence of cholecystokinin on insulin output from isolated perifused pancreatic islets. 352 23

A lipoprotein-induced resistance to the action of insulin has been postulated. To test this hypothesis, cultured rat-derived hepatoma cells, designated FAO, and human-derived hepatoma cells, designated HEP-G2, were incubated for 20 h in the presence or absence of lipoprotein; specific 125I-insulin receptor binding and labeled glucose incorporation into glycogen were then measured. Very low density lipoproteins (d less than 1.006 g/ml) in physiologic (0.5 mg/ml) or pathophysiologic (5 mg/ml) concentrations did not modify insulin receptor binding of FAO or HEP-G2 cells. This was true for very low density lipoproteins derived from normal human, diabetic human, and streptozotocin-diabetic rat plasma. Low density lipoproteins (d = 1.019 - 1.063 g/ml) isolated from normal human plasma similarly failed to modify insulin receptor binding. Concerning insulin action, the different very low density lipoprotein preparations did not modulate either basal or insulin-stimulated glucose incorporation into glycogen of the cells. Thus, very low density lipoproteins and low density lipoproteins did not induce insulin resistance in cultured hepatoma cells either at the insulin receptor level or at the post-receptor level.
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PMID:Lack of a lipoprotein-induced insulin resistance in hepatoma cells in culture. 352 46

Insulin and the insulinlike growth factors (IGF-I and IGF-II) are members of a family of hormones that regulate the metabolism and growth of many tissues. Cultured HEP-G2 cells (a minimal deviation human hepatoma) have insulin receptors and respond to insulin by increasing their glycogen metabolism. In the present study with HEP-G2 cells, we used 125I-labeled insulin, IGF-I, and IGF-II to identify distinct receptors for each hormone by competition-inhibition studies. Unlabeled insulin was able to inhibit 125I-IGF-I binding but not 125I-IGF-II binding. A mouse monoclonal antibody to the human insulin receptor that inhibits insulin binding and blocks insulin action inhibited 75% of 125I-insulin binding, but inhibited neither 125I-IGF-I nor 125I-IGF-II binding. When glycogen metabolism was studied, insulin stimulated [3H]glucose incorporation into glycogen in a biphasic manner; one phase that was 20-30% of the maximal response occurred over 1-100 pM, and the other phase occurred over 100 pM-100 nM. The anti-receptor monoclonal antibody inhibited the first phase of insulin stimulation but not the second. Both IGF-I and IGF-II stimulated [3H]glucose incorporation over the range of 10 pM-10 nM; IGF-I was three to fivefold more potent. The monoclonal antibody, however, was without effect on IGF regulation of glycogen metabolism. Therefore, these studies indicate that insulin as well as the IGFs at physiological concentrations regulate glycogen metabolism in HEP-G2 cells. Moreover, this regulation of glycogen metabolism is mediated by both the insulin receptor and the IGF receptors.
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PMID:Dual regulation of glycogen metabolism by insulin and insulin-like growth factors in human hepatoma cells (HEP-G2). Analysis with an anti-receptor monoclonal antibody. 609 May 2

A water-soluble metabolite, isolated from the urine of dogs given (S)-5-ethyl-5-phenylhydantoin [(S)-EPH], has been identified as 1-deoxy-1-[(5S)-5-ethyl-5-phenylhydantoin-3-yl] beta-D-glucopyranuronate [(S)-EPH N-glucuronide]. EPH N-glucuronide did not release the aglycone upon acid or beta-glucuronidase treatment, but incubation in alkaline solution (pH 12-13) readily formed 2-ethyl-2-phenylhydantoic acid (EPHA). The EPHA so formed could be quantitatively cyclized to EPH. With the knowledge of the conversion efficiency of EPH N-glucuronide to EPHA, a quantitative GLC assay for the metabolite was developed. EPH N-glucuronide was found to be the major urinary metabolite after administration to dogs of either (R)-, (S)-, or (RS)-EPH.
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PMID:5-ethyl-5-phenylhydantoin N-glucuronide, the major urinary metabolite of 5-ethyl-5-phenylhydantoin (Nirvanol) in the dog. 613 Sep 6

Groups of four 6- to 12-month-old male goats were injected intraruminally with a lethal dose (3 mg/kg of body weight) of aflatoxin B1 (AFB1). Drugs were administered parenterally before (pretreatment) or beginning 8 hours after goats were doses with AFB1. These drugs were phenobarbital (PB), phenylbutazone (PBZ), piperonyl butoxide (PRO), benzoflavones, water, and 5% glucose solution (D5W). Most groups given the drugs after AFB1 was administered also were given intraperitoneal injections of methionine-sodium thiosulfate (MET-TS) solution. Clinical signs of toxicosis, serum aspartate aminotransferase activities, serum bilirubin concentrations, duration of illness, mortality, and gross and microscopic pathologic findings taken together indicated that toxicosis was increased with MET-TS + PB therapy, PBZ pretreatment, PBZ therapy, benzoflavone pretreatment, benzoflavone therapy, MET-TS + benzoflavone therapy, and MET-tS + water therapy. Toxicosis was not altered appreciably by MET-TS + PBO therapy. Beneficial effects (less severe toxicosis) were produced by PB pretreatment; these effects were prolonged maintenance of strength, vigor, and appetite and (in 1 goat that recovered) absence of pathologic changes or serum bilirubin increase. Therapy with MET-TS + D5W (but not MET-TS alone) also lengthened maintenance of strength, vigor, and appetite, but did not prevent pathologic changes. The beneficial effect of MET-TS therapy reported in a previous study (AFB2 dosage of 4 mg/kg) was not observed with the 3 mg/kg lethal dose. In conclusion, therapy for acute aflatoxicosis with inducers of hepatic microsomal enzymes is ineffective (PBO) or contraindicated (PB, PBZ, benzoflavones). Therapy with D5W may be a useful adjunct to other therapeutic drugs, but multiple intraperitoneal injections of D5W may decrease survival time because of stress.
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PMID:Effect of some enzyme inducers, fluids, and methionine-thiosulfate on induced acute aflatoxicosis in goats. 680 46

We investigated cardiovascular and metabolic responses in 23 healthy pregnant volunteers in their third trimester prior to, during, and after a 15-minute period of treadmill exercise. The energy utilization of this exercise was 2.33 MET with an oxygen consumption under 0.5 L/minute. Exercise induced a significant increase in maternal heart rate and a shortening of the R time intervals; both returned to baseline by 30 minutes of recovery. This light exercise also induced a significant increase in glucagon, norepinephrine, and epinephrine concentrations, all of which were transitory and reversed within 30 minutes of the recovery period. No change in glucose or cortisol concentration resulted from this exercise. We conclude that light exercise of brief duration elicits appropriate and transitory cardiovascular and metabolic responses in normal pregnancy.
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PMID:I. Maternal cardiovascular and metabolic responses in normal pregnancy. 701 63


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