Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of somatostatin and eighteen somatostatin analogues on pentagastrin-stimulated gastric acid and pepsin secretion was investigated in the conscious vagotomized cat prepared with chronic gastric fistulae. The majority of the analogues are peptides where D-amino acids are incorporated into the molecule instead of the natural L-isomers. 2. The ID50 for cyclic-somatostatin inhibition of near-maximal gastric acid secretion stimulated by pentagastrin 8 microgram kg-1 hr-1 was found to be 1.29 +/- 0.13 n-mole kg-1 hr-1. Pentagastrin-stimulated pepsin secretion had a lower threshold to somatostatin inhibition than did acid secretion. 3. D-Phe6, D-Phe7, D-Thr10, D-Thr12 and D-Phe6-D-Trp8 analogues all show low biological activity against the secretion of gastric acid and pepsin, growth hormone, insulin and glucagon. None of these analogues are antagonists of the cyclic-somatostatin inhibition of gastric secretion, suggesting that they have low affinity for this somatostatin receptor. 4. The analogues under investigation show parallel changes in activity against gastric and growth hormone secretion, suggesting a similarity between the gastric and growth hormone receptors for somatostatin. 5. D-Cys14 analogues are equipotent with or have a greater potency than cyclic-simatostatin in inhibiting the secretion of gastric acid, growth hormone and glucagon but show low insulin inhibiting activity.
 ...
PMID:Structure-activity relationships of eighteen somatostatin analogues on gastric secretion. 34 35

Protamine-125I-insulin with low specific radioactivity was prepared using 125, 127I-insulin, 0.2 I/mole. The preparations were characterized by disc electrophoresis, isoelectric focusing and analytical gel chromatography in order to evaluate the suitability of 125I-insulin as marker for insulin in protamine-insulin. The stability of the preparations was followed up to 90 days at 4 degrees C. The biological and immunological activity was determined in mice, isolated rat fat cells and by radioimmunoassay. It was concluded that both from a chemical and a biological point of view, the protamine-125I-insulin is a satisfactory preparation that might be used in absorption studies.
 ...
PMID:Absorption of protamine-insulin in diabetic patients. I. Preparation and characterization of protamine-125I-insulin. 43 86

Patients manifesting the syndrome of cachexia of malignancy exhibit an abnormal diabetic glucose tolerance. In our patients this has been correlated with a marked resistance to administered insulin, while insulin receptors on monocytes are normal. Lipolysis remains responsive to the effects of insulin. The oxidation of FFA, as a substrate for metabolism, has been reported to be increased, and the utilization of glucose as a metabolic fuel is reduced. Increased Cori cycle activity has been demonstrated, which produces an enhanced gluconeogenesis from lactate and amino acids; there is an expenditure of 6 ATP for the synthesis of each mole of glucose. An attempt to interrupt the Cori cycle in man, using hydrazine sulfate to inhibit the enzyme phosphoenolpyruvate carboxykinase, has not resulted in reproducible clinical benefit. However, successful treatment of the underlying tumor may produce a total reversal of the cachexia syndrome, suggesting that neoplasms have the potential to elaborate an, as yet, unidentified metabolic toxin. The use of insulin to counteract the reported abnormalities should be examined as a possible supportive measure in the total nutritional management of the cancer patient.
 ...
PMID:Cachexia of malignancy: potential role of insulin in nutritional management. 44 87

A new double-labelling procedure for amino acid analysis which requires only routine chromatographic equipment is described. When 1-fluoro-2,4-dinitro[3H]benzene is reacted with a mixture of 14C-labelled amino acids followed by reaction with the same 14C-labelled amino acid mixture diluted with an unlabelled sample of amino acids, the 3H:14C ratio in the resulting 2,4-dinitrophenyl (DNP) amino acid derivatives of the diluted sample will be increased in proportion to the quantity of unlabelled amino acid in the diluted sample. This procedure gave reliable results when applied to the known proteins insulin and lysozyme. The procedure is most advantageous when applied to amino acids which are unstable during acid hydrolysis or present in low molar fractions. When applied to the analysis of the bacteriorhodopsin in Halobacterium cutirubrum, this procedure showed the presence of one histidine residue and four tryptophan residues per mole protein but no cystine or cysteine; in general, the analyses obtained were consistent with those originally reported by Oesterhelt, D. and Stoeckenius, W. (1971) (Nature (London) New Biol. 233, 149-152) for bacteriorhodopsin of H. halobium.
 ...
PMID:A new double-labelling procedure for determination of amino acid composition: application to bacteriorhodopsin. 66 97

Beta-Cell-rich pancreatic islets microdissected from obese-hyperglycemic mice were used to study interactions between the metabolism of L-leucine and D-glucose. L-leucine reduced the islet content of aspartic acid whereas D-glucose, when added to L-leucine-incubated islets, increased the contents of aspartic acid and gamma-aminobutyric acid (GABA). D-glucose also increased the incorporation of L-leucine carbon into aspartic acid, GABA and glutamic acid suggesting stimulation of a malate shuttle mechanism. When expressed per mole of the individual amino acids, the incorporation of L-leucine carbon into GABA was 2.5-4 times higher than into glutamic acid indicating intracellular compartmentation of the latter amino acid. Both L-leucine and D-leucine stimulated 14CO2 production from 14C-labelled D-glucose. L-leucine did not affect 3H2O production from tritiated D-glucose. The present data do not indicate a role of other amino acids or D-glucose in L-leucine-stimulated insulin release.
 ...
PMID:Interactions between the metabolism of L-leucine and D-glucose in the pancreatic beta-cells. 76 54

1. Fluxes of 45Ca2+ were studied in pancreatic islets from non-inbred ob/ob-mice. Because La3+ blocked the transmembrane fluxes of 45Ca2+ in islet cells, incubations aimed at measuring glucose-induced changes of the intracellular Ca2+ were ended by washing the islets with 2 mM-La3+ for 60 min. 2. Uptake of 45Ca2+ progressed for 2 hr; the intracellular concentration of exchangable Ca2+ was about 7 m-mole/kg dry wt., as estimated from the isotope distribution at apparent equilibrium in islets exposed to 3 mM D-glucose. Raising the D-glucose concentration to 20 mM enhanced the 45 Ca2+ uptake whether or not the islets had first been equilibrated with the isotope. The stimulatory effect of D-glucose was observed in Tris buffer containing no anions but Cl- as well as in polyanionic bicarbonate buffer. The effect could not be reproduced with equimolar L-glucose. 3. The rate of 45Ca2+ release was the same whether the islets had been pre-loaded in the presence of 3 or 20 mM D-glucose. Thus the 45Ca2+ that had been taken up in response to 20 mM D-glucose appeared to be released much more slowly than the bulk of intracellular 45Ca2+. The release of 45Ca2+ was not significantly influenced by D-glucose during the release period. Incubation for 30 min was require for half of the radioactivity to be released. 4. The rates of insulin secretion were about the same in uni-anionic Tris buffer as in polyanionic bicarbonate buffer. A marked insulin secretory response to 20 mM D-glucose was observed in either buffer. 5. It is concluded that 20 mM D-glucose causes a net uptake of Ca2+ from the extracellular fluid into the interior of the beta-cells. This uptake is probably not regulated at the level of the plasma membrane but more likely reflects an increased affinity of some intracellular phase or compartment for the ion. Because the observed uptake and release of intracellular 45Ca2+ are slow processes in comparison with the rapid effects of extracellular Ca2+ on insulin secretion, insulin secretion may also depend on a more superficial and La3+-displacable Ca2+ pool.
 ...
PMID:Effects of glucose on 45Ca2+ uptake by pancreatic islets as studied with the lanthanum method. 76 50

Macromolecules have been prepared containing native insulin carried by a modified insulin skeleton made by partially thiolating the insulin hexamer and forming intermolecular cross-links through disulphide bridges. Oxidation of partially thiolated insulin (0.5-0.7 SH group/mole), formed by reacting insulin with AHTL, with, (a) potassium ferricyanide, (b) Cu++-oxygen gave water soluble macromolecules containing 20-26 and 410-708 monomer units respectively which had rod-random coil shape (light scattering). The larger molecules formed by (b) contained 8g-atom CU++/hexamer unit and insulin. The insulin was firmly bound within the marcomolecules and was probably bound within an insulin-modified insulin hexamer through coordination to copper.
 ...
PMID:Thiolation and disulphide cross-linking of insulin to form macromolecules of potential therapeutic value. 92 May

Plasma HCS levels have been measured in normal and pathological pregnant women. In the normal group HCS levels increased from 6--8 weeks till 33-34 weeks and then felt significantly. HCS pattern in prediabetic and chemical diabetic pregnant women was similar to the normal group. However HCS levels in chemical diabetics were significantly higher during the first two trimesters. HCS levels increased in twin pregnancy, diminished in cases of eclampsia, hypertension, fetal growth retardation, mole and blighted ovum, and disappeared after intrauterine death. Nothing could be deduced from the obese and Rh-isoimmunization groups. It is confirmed the value of HCS determination as an index of placental maturation. Also, insulin/HCS ratio may be of some aid in the study of carbohydrate intolerance in pregnancy.
 ...
PMID:Human chorionic somatommamotropin (HCS) and pregnancy. Its relation with insulin. 103 1

To assess the metabolic effects of myocardial substrate alteration in patients with coronary artery disease, glucose-insulin-potassium solution was administered intravenously for 30 minutes to 14 men with stable angiographically documented coronary artery disease. The glucose-insulin-potassium solution (300 g of glucose, 50 units of regular insulin and 80 mEq of potassium chloride per liter of water) was infused at a constant rate in each patient, but individual infusion rates ranged from 0.013 to 0.032 ml/kg per min (4 to 10 mg glucose/kg per min) in the 14 patients. Simultaneous arterial and coronary sinus samples were obtained at 15 minute intervals during a stable 30 minute control period and again at 15 minute intervals during the infusion; samples were assayed for glucose, lactate, free fatty acid and oxygen content. In all 14 patients, during the glucose-insulin-potassium infusion, arterial glucose and lactate increased and arterial free fatty acid levels fell; the magnitude of the changes in arterial lactate and free fatty acids was related to the rate of infusion. Arterial-coronary sinus differences (A-Cs) for glucose, lactate and free fatty acid levels correlated with the arterial concentrations of these substrates (r = 0.66, 0.87 and 0.79, respectively). Regression analyses demonstrated myocardial thresholds for the uptake of these substrates as follows: glucose 79 mg/100 ml; lactate 300 mu mole/liter; and free fatty acids 100 to 200 mu Eq/liter. Finally and most importantly, the reduction in A-Cs oxygen values after glucose-insulin-potassium infusion correlated with the reduction in A-Cs free fatty acid levels (r = 0.64, P less than 0.0001). This observation suggests that, in patients with coronary artery disease, glucose-insulin-potassium infusion may significantly diminish myocardial oxygen requirements by reduction of myocardial free fatty acid utilization and simultaneous enhancement of myocardial carbohydrate utilization. Myocardial substrate availability may be an important determinant of myocardial oxygen demand in patients with coronary artery disease. Infusion of glucose-insulin-potassium solution has the potential to alter myocardial substrate availability, thus improving the balance between myocardial oxygen demand and supply.
 ...
PMID:Effects of glucose-insulin-potassium on myocardial substrate availability and utilization in stable coronary artery disease. Studies on myocardial carbohydrate, lipid and oxygen arterial-coronary sinus differences in patients with coronary artery disease. 119 50

Based on the clinicopathological classification of distinct stages of tumor progression in the melanocytic system, we have investigated the in vitro growth patterns and requirements of normal melanocytes and melanocytes isolated from different lesions of melanoma progression. Normal melanocytes depend on a combination of insulin-like growth factor (IGF-I) or insulin, 12-O-tetradecanoyl phorbol-13-acetate (TPA), alpha-melanocyte stimulating hormone (alpha-MSH), and basic fibroblast growth factor (bFGF) for in vitro proliferation. Nevus cells display a reduced need for TPA and are largely independent of bFGF. Both melanocytes and nevus cells have a finite lifespan in vitro and show no spontaneous transformation, whereas melanoma cells can be grown indefinitely in vitro. Cells from primary melanomas require only IGF-I or insulin for continuous growth, and metastatic melanoma cells can proliferate in base medium without addition of any growth factors or proteins. This progressive growth autonomy is paralleled by an increased competence for endogenous growth factor production. Among these growth factors, bFGF and melanoma growth-stimulatory activity (MGSA) act in an autocrine fashion. Melanoma-derived growth factors without apparent autocrine function, such as platelet-derived growth factor A and B (PDGF-A and PDGF-B) and transforming growth factor-alpha (TGF-alpha), might still be important for melanoma growth by stimulating surrounding normal fibroblasts, endothelial cells, or keratinocytes to secrete growth-promoting factors. The significance of growth factors such as transforming growth factor-beta (TGF-beta) and melanoma-inhibiting activity II (MIA II), which have a potentially negative autocrine function, remains unknown. The successful propagation of melanocytic cells of all stages of melanoma progression has yielded valuable insight into the mechanisms of growth regulation and malignant transformation.
 ...
PMID:In vitro growth patterns of normal human melanocytes and melanocytes from different stages of melanoma progression. 144 12


1 2 3 4 5 6 7 8 9 10 Next >>