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 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Change in aggregation state of insulin upon conjugation with 5-dimethylaminonaphthalene-1-sulfonyl (DNS) group was investigated at neutral pH. DNS group was introduced exclusively into B1 phenylalanine, the N-terminus of the B-chain of insulin. The association state of insulin shifted toward a more highly aggregated one upon conjugation, depending on the mole fraction (d) of DNS group to insulin monomer; at d equal 0.3 the equilibrium between dimer and hexamer was dominant over the range of 1-600 microM, while at d equal 1.0-1.5 DNS-insulin formed a larger aggregate (dodecamer) which is stable over the range of 67-600 microM. The dissociation constant of dimer-hexamer equilibrium at d=0.3 was evaluated to be 2.5 x 10(-10) M2 from the fluorescence anisotropy of the DNS group, which was about one order of magnitude smaller than that of the dimer-hexamer equilibrium in native insulin. Spectroscopic data and fluorescence decay analyses indicated that there exist at least two different environments surrounding the dye bound to B1 phenylalanine and that they are both relatively hydrophilic. It is considered that the major part of DNS group has excitation and emission maxima at longer wavelength with relatively low quantum yield, while the minor part has excitation and emission maxima at shorter wavelengths with relatively high quantum yield. The fluorescence lifetime of the dye was modified by the change in quaternary structure of DNS-lifetime of the dye was modified by the change in quaternary structure of DNS-insulin. Remarkable depolarization of DNS fluorescence was observed at d equal 1.0 and d equal 1.5 due to energy transfer between DNS groups conjugated to B1 phenylalanine in the hexamer or the dodecamer. Critical transfer distance for inter-DNS energy transfer was evaluated to be 15 A. From the molecular model of the insulin crystal, this energy transfer is ascribed to the close proximity, within about 15 A, between DNS groups in dimer units of the hexamer or the dodecamer.
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PMID:Change in aggregation state of insulin upon conjugation with 5-dimethylaminonaphthalene-1-sulfonyl group. 636 Oct 12

A single exposure to a low concentration (10(-9) mole/l) of exogenous arachidonic acid or of prostaglandins of A, E, and F series significantly stimulated primary neonatal rat hepatocytes to enter S phase irrespective of whether the extracellular calcium concentration was high (i.e., 1.8 mmole/l) or markedly reduced (i.e., 0.01 mmole/l). Similarly, a single treatment with an even smaller (10(-10) mole/l) dose of the known tumor promoters 12-O-tetradecanoylphorbol-13-acetate (TPA), phenobarbital, and nafenopin enhanced hepatocytic DNA synthesis when the environmental calcium level was both high and low. By contrast, a single application of a small concentration (10(-11)-10(-10) mole/l) of hormones such as epidermal growth factor (EGF), glucagon, and insulin, and of drugs such as imidazole and indomethacin only increased the hepatocytic flow into DNA synthesis when the extracellular calcium was high. These findings reveal that the mechanisms of physiological or pharmacological, calcium-dependent stimulation of hepatocellular growth are likely to be different from those of pathological, calcium-independent stimulation, as the latter, but not the former, would involve prostaglandin-mediated metabolic processes.
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PMID:The tumor promoters TPA, phenobarbital, and nafenopin and the prostaglandins of A, E, and F series overcome the G1/S block imposed by extracellular calcium deprivation on neonatal rat hepatocytes. 658 44

When isolated rat pancreatic islets are exposed to L-leucine (20 mM), the rate of NH4 production is close to the summed rates of L-[1-14C] leucine decarboxylation and alpha-ketoisocarproate production, whereas the rates of acetoacetate production and L-[U-14C]-leucine oxidation are compatible with conversion of each mole of the amino acid to one mole of acetoacetate and three moles of CO2. ATP content, ATP/ADP ratio, and adenylate charge are maintained at normal values by L-leucine, whereas the NADH/NAD+ ratio (but not the NADPH/NADP+ ratio) is significantly increased. The release of insulin evoked by L-leucine is potentiated by 2-ketoisovalerate, unaffected by L-valine, and inhibited by menadione. L-leucine mimicks the effect of D-glucose on 86Rb+ and 45Ca2+ handling by the islets. However, relative to its rate of oxidation, the insulinotropic effect of L-leucine is less marked than that of D-glucose. This may be due, in part at least, to a decrease in the oxidation of endogenous nutrients. It is concluded that the metabolic, cationic, and secretory effects of L-leucine in isolated islets are not incompatible with the fuel hypothesis for insulin release.
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PMID:The stimulus-secretion coupling of amino acid-induced insulin release: metabolism and cationic effects of leucine. 676 28

Adaptations of energy metabolism, as they occur during contractions of skeletal muscle besides by anaerobic glycolysis are achieved via changes in capillary blood flow providing substrates and oxygen for combustion. Since, initially, oxygen supply is restricted in the working muscle, glucose would seem to be the adequate fuel as it may be used anaerobically and yields more energy per mole of oxygen than fatty acids under such circumstances. Besides glucose, amino acids are also required for accelerated proteosynthesis according to the work load. Therefore, an enlargement of the capillary net has to be accompanied by an amplification of the action of insulin, which is often present in only small amounts, e.g., after an overnight fast. This aim is met in three ways: (1) enlargement of the capillary net with accelerated blood flow increasing the supply of insulin and the number of receptor sites for insulin binding; (2) accelerated transport of insulin through the capillary wall, providing more insulin in the interstitial space and at the plasma membranes; (3) a molecular mechanism directly involving the insulin-receptor-messenger complex, localized at the plasma membrane of the working muscle cell. These mechanisms resemble a self-regulatory process, set in motion by the release of metabolites from the working tissue. From recent studies there is accumulating evidence that kinins liberated from their precursors are involved as tissue hormones by carrying the signal across the interstitial space to the smooth muscle cells of the capillary vessels. Concomitantly, prostaglandins are released intracellularly to bring about, in cooperation with kinins, the various adaptive mechanisms. Amplifying systems of this kind may play a role not only in muscle but also in other tissues where adequate kinin or prostaglandin release would appear beneficial under several clinical conditions such as shock, coronary infarction, wound healing, etc.
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PMID:[New aspects of the blood flow-augmenting and insulin-like activity of muscle exercise: possible involvement of the kallikrein-kinin-prostaglandin system (author's transl)]. 680 24

Cell aggregates of bovine parathyroid tissue were prepared by limited collagenase digestion and placed in culture in Weymouth's MB752/1 (calcium = 3.3 mg/100 ml) containing 5% fetal bovine serum and supplemented with insulin alone, or insulin, hydrocortisone, transferrin and epidermal growth factor. Only insulin was required for the maintenance of PTH secretion over a 9-day period. The cell aggregates spread to form monolayer in 3-5 days. The majority of the cells in monolayer were polygonal with well-defined borders. Nuclei were round and the cytoplasm was free of vacuoles. Cell cultures responded to secretory stimulation by low calcium or by isoproterenol with increases in the secretion of PTH and SP-1. At low calcium, about 18% of both the cellular PTH and SP-1 was secreted per hour, and up to 50% of the cell content of these proteins was released per hour upon stimulation by isoproterenol and low calcium combined. The responses to calcium and isoproterenol decreased as a function of time in culture, and calcium responses often disappeared completely by 10 days of culture. When cells were cultured in medium containing a higher (5 mg%) than standard concentration of calcium between days 3-6 of culture, the degree of secretory inhibition attainable with high calcium was greater than that of cells cultured in the standard medium. When secreted hormonal peptides were separated by SDS-gel electrophoresis prior to RIA, it was found that the secretion of intact hormone was sensitive to calcium. For every molecule of PTH secreted into the medium, 1.5-2 mole-equivalents of carboxyl fragments were also released. Calcium control of fragment release was not as stringent as that of PTH release.
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PMID:Primary monolayer cell culture of bovine parathyroids: effects of calcium, isoproterenol and growth factors. 686 97

1. The effects of insulin hypoglycaemia on cerebral blood flow and metabolism have been examined in unanaesthetized, unrestrained calves between 1 and 26 days after birth. 2. Cerebral blood flow was measured with an inert gas technique using molecular hydrogen, and cerebral metabolism was quantified by determination of arterio-cerebral venous (A--V) concentration differences for oxygen, glucose, lactate, pyruvate, acetoacetate, beta-D-hydroxybutyrate and ammonia. 3. During normoglycaemia the mean (A--V) difference for glucose was close to one sixth that of oxygen, on a molar basis. A small net loss of pyruvate from the brain was found, but there was no significant (A--V) difference for lactate. Arterial concentrations of acetoacetate and beta-D-hydroxybutyrate were low, and no utilization of ketone bodies by the brain was demonstrated. 4. Moderate hypoglycaemia (arterial plasma glucose concentration 1--2 m-mole/l.) had no measurable effect on either cerebral blood flow or metabolism. 5. During profound hypoglycaemia (arterial plasma glucose concentration less than 1.0 m-mole/l.) cerebral glucose uptake was sufficient to account for only 56% of the cerebral oxygen consumption. Cerebral oxygen consumption fell in comatose animals, but increased during hypoglycaemic convulsions, as did cerebral blood flow. 6. In day-old calves hypoglycaemia was associated with a rise in blood lactate concentration and uptake of lactate by the brain. 7. A net loss of ammonia by the brain was observed during hypoglycaemia in calves at all ages examined. The loss was greater in convulsing than in comatose animals.
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PMID:The effects of hypoglycaemia on cerebral blood flow and metabolism in the new-born calf. 698 78

1. The effects of autonomic stimulation on the release of vasoactive intestinal peptide (VIP) from the gastrointestinal tract have been investigated in adrenalectomized claves 2-5 weeks after birth.2. Stimulation of the peripheral ends of the splanchnic nerves (10 Hz for 10 min) caused a small fall in the concentration of VIP in portal and arterial plasma, together with a rise in the concentration in intestinal lymph. None of these changes achieved statistical significance.3. The effects of stimulation of the peripheral ends of the thoracic vagi, below the heart (10 Hz for 10 min), were found to depend in part upon the integrity of the splanchnic sympathetic innervation. A substantial rise in the concentration of VIP in intestinal lymph occurred whether or not the splanchnic nerves had been cut whereas an associated rise in arterial plasma VIP was only observed in calves in which the splanchnic nerves had been sectioned.4. The rise in the concentration of VIP in intestinal lymph, in response to vagal stimulation, was unaffected by concomitant stimulation of the splanchnic nerves, although the associated rise in arterial plasma VIP concentrations was suppressed. The response was also found to be resistant to atropine.5. The minimum estimated concentration of VIP in the extracellular fluid of the gastrointestinal tract was estimated to be about 60 p-mole/l. at rest and to rise by 70-120 p-mole/l. in response to vagal stimulation.6. Intravenous infusions of VIP at a dose of 50 ng kg(-1) min(-1) (16 p-mole kg(-1) min(-1)), which raised the minimum estimated concentration of VIP in the gastro-intestinal tract to the highest range encountered during stimulation, produced no significant changes in the concentrations of glucose, insulin, pancreatic glucagon or pancreatic polypeptide in the arterial plasma.7. It is concluded that a small amount of VIP is released from the gastrointestinal tract in response to vagal stimulation. In contrast, release of VIP is unaffected by stimulation of the splanchnic nerves except in so far as the rate at which the peptide passes into the circulation is reduced by adrenergic vasoconstriction.
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PMID:Effects of autonomic stimulation on the release of vasoactive intestinal peptide from the gastrointestinal tract in the calf. 699 67

The contribution of the insulin A- and B-chain to the retention and bandwidth behaviour of bovine insulin has been investigated. The influence of temperature and residence time on the logarithmic capacity factor (log k) versus the mole fraction of organic modifier psi, i.e. the effect of temperature and ligand residency on the S and log k0 values of the individual peptide chains, were assessed at temperatures between 5 and 85 degrees C and elution times between 30 to 90 min with an n-octadecyl (C18) and an n-butyl (C4) sorbent. Analysis of these log k versus psi dependencies revealed that the insulin A-chain exhibits retention behaviour significantly different to the intact insulin molecule whilst the B-chain exhibits retention behaviour which is remarkably similar to the parent protein. However, in terms of kinetic processes, the A-chain exhibited a peak-splitting phenomenon at higher temperatures which was similar to the behaviour of the intact insulin molecule, whilst only bandbroadening with no peak splitting was apparent for the B-chain. Overall, the similarity of the retention behaviour of the insulin B-chain and the intact insulin molecule with regard to their temperature and residency dependencies suggests that the insulin B-chain makes a significant contribution to the chromatographic contact region of the insulin molecule when this polypeptide is exposed to hydrocarbonaceous ligands at low to intermediate temperatures due to the progressive unfolding of the molecule and greater accessibility of the previously buried B-chain residues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Conformational effects in reversed-phase high-performance liquid chromatography of polypeptides. II. The role of insulin A and B chains in the chromatographic behaviour of insulin. 749 96

A low-cost and highly sensitive laser-induced fluorescence detector for on-column detection systems was constructed and its applications were demonstrated in protein separation by capillary electrophoresis. The limit of detection (LOD) at a signal-to-noise ratio of 2 for Lissamine 20 was about 1.4 x 10(-21) mole at 10 nL sample injection and the relative standard deviation (RSD) for 1.5 x 10(-11) M of Lissamine 20 solution was about 15%. These values are comparable to or even better than those reported using a similar on-column detection system. This sensitive LIF detection was applied for the study of tryptic digestion of insulin and for urinary protein profiling.
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PMID:Simple and sensitive laser-induced fluorescence detection for capillary electrophoresis and its application to protein separation. 758 43

Vipera berus berus venom contains several factor X activating enzymes. One of them (VBFXAE) was separated by gel-filtration on Sephadex G-100 superfine and on a bacitracin-agarose column. The enzyme is a single-chain glycoprotein with mol. wt 38,000. The enzyme has several molecular forms with pI 3.5-4.5. After neuraminidase treatment the enzyme has pI 4.5. VBFXAE contains 2 Ca per mole. The activator is inactive on synthetic substrates, on casein, prothrombin, and fibrinogen, and appears to act specifically on factor X. The activator also weakly hydrolyses the insulin B-chain at the positions Ala14-Leu15 and Tyr16-Leu17. The cleavage of the insulin B-chain is inhibited by EDTA, suggesting the metalloproteinase nature of the enzyme.
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PMID:Medium molecular weight factor X activating enzyme from Vipera berus berus venom. 777 28


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