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  • HIOMT  (8)
  • 5-methoxyindoles  (6)
  • lipolysis  (5)
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  • 1
    ISSN: 1432-0428
    Schlagwort(e): Substrate oxidation ; energy expenditure ; lipolysis ; ketogenesis ; “dawn” phenomenon
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I (IGF-I) administration. The aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healthy male subjects (age 27±4 years, BMI 21.8±1.7 kg/m2) were treated with NaCl 0.9% (saline) or IGF-I (8 Μg · kg−1 · h−1) for 5 days by continuous subcutaneous infusion in a randomized, crossover fashion while receiving an isocaloric diet (30 kcal · kg−1 · day−1). On the third treatment day an intravenous bolus of 0.5 U GH was administered. Forearm muscle metabolism was examined by measuring arterialized and deep venous blood samples, forearm blood flow by occlusion plethysmography and substrate oxidation by indirect calorimetry. IGF-I treatment significantly reduced insulin concentrations by 80% (p〈0.02) and C-peptide levels by 78% (p〈0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA), glycerol and 3-OH-butyrate levels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10±0.43 (saline) to 2.79±0.37 ml · 100ml−1 · min−1 (IGF-I) (p〈0.02). GH-pulse: 10 h after i.v. GH injection serum GH peaked at 40.9±7.4 ng/ml. GH did not influence circulating levels of total IGFI, C-peptide, insulin or glucose, but caused a further increase in NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose from 702±267 (saline) and 885±236 (IGF-I) to 963±215 (saline) (p〈0.05) and 1815±586 Μmol/l (IGF-I) (p〈0.02), respectively; after 5 h, 3-OH-butyrate rose from 242±234 (saline) and 340±280 (IGF-I) to 678±638 (saline) (p〈0.02) and 1115±578 Μmol/l (IGF-I) (p〈0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only in the subjects treated with IGF-I: from 44±195 to 300±370 after 20 min (p〈0.03) and to 287±91 nmol · 100 ml−1 · min−1after 120 min (p〈0.02). In conclusion, the lipolytic and ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased.
    Materialart: Digitale Medien
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): Keywords Substrate oxidation ; energy expenditure ; lipolysis ; ketogenesis ; “dawn” phenomenon.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Growth hormone (GH) secretion is suppressed during insulin-like growth factor-I (IGF-I) administration. The aim of the study was to examine whether IGF-I alters the metabolic response to a GH pulse. Seven healthy male subjects (age 27 ± 4 years, BMI 21.8 ± 1.7 kg/m2) were treated with NaCl 0.9 % (saline) or IGF-I (8 μg · kg–1· h–1) for 5 days by continuous subcutaneous infusion in a randomized, crossover fashion while receiving an isocaloric diet (30 kcal · kg–1· day–1). On the third treatment day an intravenous bolus of 0.5 U GH was administered. Forearm muscle metabolism was examined by measuring arterialized and deep venous blood samples, forearm blood flow by occlusion plethysmography and substrate oxidation by indirect calorimetry. IGF-I treatment significantly reduced insulin concentrations by 80 % (p 〈 0.02) and C-peptide levels by 78 % (p 〈 0.02), as assessed by area under the curve. Non-esterified fatty acid (NEFA), glycerol and 3-OH-butyrate levels were elevated and alanine concentration decreased. Forearm blood flow rose from 2.10 ± 0.43 (saline) to 2.79 ± 0.37 ml · 100ml–1· min–1 (IGF-I) (p 〈 0.02). GH-pulse: 10 h after i. v. GH injection serum GH peaked at 40.9 ± 7.4 ng/ml. GH did not influence circulating levels of total IGF-I, C-peptide, insulin or glucose, but caused a further increase in NEFA, glycerol and 3-OH-butyrate levels, indicating enhanced lipolysis and ketogenesis. This effect of GH was much more pronounced during IGF-I: NEFA rose from 702 ± 267 (saline) and 885 ± 236 (IGF-I) to 963 ± 215 (saline) (p 〈 0.05) and 1815 ± 586 μmol/l (IGF-I) (p 〈 0.02), respectively; after 5 h, 3-OH-butyrate rose from 242 ± 234 (saline) and 340 ± 280 (IGF-I) to 678 ± 638 (saline) (p 〈 0.02) and 1115 ± 578 μmol/l (IGF-I) (p 〈 0.02) respectively. After injection of GH, forearm uptake of 3-OH-butyrate was markedly elevated only in the subjects treated with IGF-I: from 44 ± 195 to 300 ± 370 after 20 min (p 〈 0.03) and to 287 ± 91 nmol · 100 ml–1· min–1after 120 min (p 〈 0.02). In conclusion, the lipolytic and ketogenic response to GH was grossly enhanced during IGF-I treatment, and utilization of ketone bodies by skeletal muscle was increased. [Diabetologia (1996) 39: 961–969]
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-0428
    Schlagwort(e): Adipocytes ; acipimox ; lipolysis ; cyclic AMP ; cyclic AMP-dependent protein kinase ; hormone-sensitive lipase ; enzyme translocation ; insulin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Acipimox is commonly used to treat hyper-triglyceridaemia in non-insulin-dependent diabetic patients, but its precise mechanism of action has yet to be elucidated. We examined the in vitro effects of acipimox on the lipolytic regulatory cascade in epididymal adipocytes isolated from Wistar rats. Acipimox inhibited the lipolytic rate stimulated by adenosine deaminase (1 U/ml) in a concentration-dependent manner, reaching a near-basal value at 10 Μmol/l acipimox. Lipolysis activated by sub-maximal levels of isoproterenol in combination with adenosine deaminase (20 mU/ml) was significantly (p〈0.05) decreased by 100 Μmol/l acipimox, whereas, in the absence of adenosine deaminase, 100 Μmol/l acipimox showed no significant (p〉0.05) inhibition. These findings suggested that the anti-lipolytic mechanism regulated by adenosine may also be regulated by acipimox. Acipimox diminished the intracellular cyclic AMP level produced by 25 nmol/l isoproterenol in the presence of adenosine deaminase (20 mU/ml) in a concentration-dependent manner. At the same level of stimulation, acipimox inhibited the cyclic AMP-dependent protein kinase activity ratio and lipolytic rate over the same concentration range, with significant (p〈0.05) reductions occurring at and above, 0.5 Μmol/l and 10 Μmol/l acipimox, respectively. Western blotting showed that upon lipolytic stimulation (1 U/ml adenosine deaminase; 100 nmol/l isoproterenol) a threefold increase in the lipolytic rate was accompanied by a significant (p〈0.05) rise in hormone-sensitive lipase associated with the lipid fraction. Acipimox (1 mmol/l) and insulin (1 nmol/l) re-distributed hormone-sensitive lipase back to the cytosol, with a corresponding significant (p〈0.05) loss from the fat cake fraction of adipocyte homogenates. In conclusion, the anti-lipolytic action of acipimox is mediated through suppression of intracellular cyclic AMP levels, with the subsequent decrease in cyclic AMP-dependent protein kinase activity, leading to the reduced association of hormone-sensitive lipase with triacylglycerol substrate in the lipid droplet of adipocytes.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1432-0428
    Schlagwort(e): Growth hormone ; insulin ; insulin deficiency ; glucagon ; blood glucose ; ketone bodies ; ketogenesis ; lipolysis ; non-esterified fatty acids
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The metabolic effects of acute (4 h) and prolonged (24 h) growth hormone excess at pathophysiological concentrations were studied by growth hormone administration to normal subjects with and without somatostatin induced insulin deficiency. Acute growth hormone excess produced mild hyperinsulinaemia, but blood glucose concentrations were unaltered whereas chronic growth hormone excess caused a small (0.5 mmol/l) but significant rise in overnight-fasting blood glucose concentration together with a similar rise in fasting insulin levels (Mean ± SEM 9 ± 1 v 4 ± 1 mU/l, p〈0.01). When insulin secretion was suppressed by somatostatin, a hyperglycaemic effect of acute growth hormone excess was unmasked, and the hyperglycaemic effect of chronic growth hormone excess was exaggerated. Acute growth hormone administration without somatostatin had a mild ketogenic action despite stimulated insulin secretion but no change in plasma non-esterified fatty acid or blood glycerol levels was observed. Somatostatin magnified the ketogenic effect of acute growth hormone excess, and unmasked a lipolytic action. Prolonged growth hormone excess had a lipolytic action that was increased by somatostatin, although the ketogenic effect of growth hormone was only seen during somatostatin induced insulin deficiency. The acute hyperglycaemic, lipolytic and ketogenic actions of growth hormone in normal subjects are limited by a compensatory rise in insulin secretion although with chronic exposure hyperglycaemic and lipolytic effects are seen. In insulin-deficient states, however, elevated growth hormone levels could be important in promoting hyperglycaemia and hyperketonaemia.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 26 (1984), S. 23-28 
    ISSN: 1432-1041
    Schlagwort(e): dopamine ; somatostatin ; insulin ; glucagon ; growth hormone ; plasma glucose ; NEFA ; lipolysis ; ketogenesis ; insulin-deficiency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The metabolic effects of dopamine have been investigated by its infusion in normal man with and without simultaneous somatostatin administration. Dopamine was infused into overnight fasted men at 1.5 µg/kg/min (n=6) and 3.0 µg/kg/min (n=5) for 120 min. Plasma dopamine concentrations at 120 min were 78±9 nmol/l and 117±17 nmol/l respectively, associated with a marginal rise in plasma noradrenaline. Dopamine (1.5 µg/kg/min) induced an early and sustained rise in plasma glucagon (48±9 pg/ml versus 19±6 pg/ml in saline controls at 10 min, p〈0.01)and a transient elevation in serum growth hormone which peaked to 17.7 (range 4.5–71.8)mU/l at 60 min (7.2 (range 0.6–37.7) mU/l with saline, p〈0.05), but did not alter serum insulin, blood glucose or other metabolite levels. At 3.0 µg/kg/min, dopamine in addition provoked mild and transient elevations in blood glucose and serum insulin. Somatostatin (250 µg/h) suppressed circulating insulin, glucagon, and growth hormone levels and abolished the small hyperglycaemic effect seen with the higher dopamine dose. Somatostatin alone induced a progressive rise in circulating non-esterified fatty acid and 3-hydroxybutyrate levels reflecting insulin deficiency. This rise in NEFA and 3-hydroxybutyrate was increased by dopamine particularly at the higher dosage (plasma NEFA; somatostatin alone, 1.08±0.13 mmol/l; somatostatin plus dopamine 3 µg/kg/min, 1.44±0.17 mmol/l at 120 min, p〈0.01: blood 3-hydroxybutyrate; somatostatin alone, 0.32±0.04 mmol/l; somatostatin plus dopamine 3 µg/kg/min, 0.56±0.12 mmol/l at 120 min, p〈0.05). Thus: 1) dopamine at pharmacological dosage has minor effects when other endocrine mechanisms are intact, 2) it enhances lipolysis and ketogenesis during somatostatin-induced insulin deficiency, 3) the hyperglycaemic effect of the higher dopamine dose is probably mediated through stimulated glucagon secretion.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1435-1463
    Schlagwort(e): Pineal ; HIOMT ; COMT ; rats
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In pineals of 10 day old rats 5-hydroxytryptophan, 5-hydroxyindole-3-acetic acid, N-acetylserotonin/5-hydroxytryptophol and norepinephrine are methylated following a circadian rhythm. During the night HIOMT and COMT activities were measured for the above mentioned substrates, while HIOMT activity for 5-hydroxytryptophan and N-acetylserotonin/5-hydroxytryptophol was also determined during daytime.
    Materialart: Digitale Medien
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  • 7
    ISSN: 1435-1463
    Schlagwort(e): Pineal ; melatonin/5-methoxytryptophol ; 5-methoxyindoles ; pteridines ; red light
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In previous investigations the change of circadian rhythmicity in pineal melatonin/5-methoxytryptophol synthesis of rats periodically exposed to red light was similar to that in pineals of rats incubated with pterin-6-aldehyde. These experiments were, however, performed with rats of different age and in different periods of the year. In the present study these two factors influencing pineal indole metabolism have been combined the experiments being carried out in rats aged 28 days and during the same day in the month of January. It was observed that under influence of red light the peak of melatonin/5-methoxytryptophol synthesis shifted towards daytime, whereas incubation with pterin-6-aldehyde did not cause such a shift. If under different experimental conditions the mean amount of melatonin/5-methoxytryptophol which was formed over a 24 hour period was compared, it appeared that pineals of rats exposed to white light incubated with reduced neopterin but not pineals incubated with pterin-6-aldehyde behave in this respect similar to pineals of rats exposed to red light. However, if the ratio between melatonin/5-methoxytryptophol and 5-methoxytryptamine is calculated pineals of white light exposed rats incubated in pterin-6-aldehyde behaved very similar to the pineals of rats exposed to red light. Although the role of pteridines remains obscure, it appears that the parameters 1. circadian rhythmicity and 2. the amount of 5-methoxyindoles and 3. the ratio between these indole derivatives might be of importance in analyzing their physiological effects. The influence of application of light of different wavelenghts and year rhythmicity is discussed.
    Materialart: Digitale Medien
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  • 8
    ISSN: 1435-1463
    Schlagwort(e): Pineal ; melatonin/5-methoxytryptophol ; 5-methoxyindoles ; pteridines ; green light
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The pineals of 28 days old male Wistar rats, in December periodically exposed to either white or green light, were incubated with pterin-6-aldehyde or reduced neopterin. In white light the rhythm of synthesis of 5-methoxytryptophan and of 5-methoxyindole-3-acetic acid was clearly influenced by the pteridines mentioned. In green light a change in rhythmicity of 5-methoxytryptophan, 5-methoxytryptamine and of melatonin/5-methoxytryptophol synthesis by the pteridines was observed. In white light both pteridines increased 5-methoxytryptophan and decreased 5-methoxyindole-3-acetic acid synthesis. Reduced neopterin stimulated 5-methoxytryptamine synthesis and inhibited melatonin/5-methoxytryptophol synthesis. Pterin-6-aldehyde showed an opposite effect. In green light both pteridines decreased 5-methoxytryptophan synthesis, but increased 5-methoxyindole-3-acetic acid and 5-methoxytryptamine synthesis. Melatonin/5-methoxytryptophol synthesis was decreased by reduced neopterin and increased by pterin-6-aldehyde. The results suggest an indolic metabolic pathway leading from 5-methoxytryptophan via 5-methoxytryptamine to melatonin, while pteridines and light of different wave lengths are correlated in regulating indole metabolism.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1435-1463
    Schlagwort(e): Pineal gland ; melatonin ; 5-methoxyindoles ; seasonal rhythmicity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Until now the day/night and seasonal rhythmicity in the synthesis of 5-methoxyindoles (MI) is thought to be regulated by environmental factors, especially photoperiod and temperature. Endogenous factors are also implicated in the generation of N-acetyltransferase and hydroxyindole-O-methyltransferase activity rhythms. In the present experiments seasonal rhythmicity in the synthesis of MI in the pineal gland was investigated in hamsters kept under the same artificial conditions throughout the year. Though the environmental conditions were the same, day/night and seasonal rhythmicity in the production of MI in the pineal were observed indicating the existence of endogenous factors influencing the rhythmicities. In November, most of the MI showed the highest synthesis, MA and ML excepted, which were especially produced in July and September. The results obtained sustain the hypothesis that aMT is synthesized from MT rather than from aHT. Moreover, the rhythmicities in aMT synthesis are not identical to those found in aMT concentration as described in the literature. This indicates that synthesis and concentration of a compound are not comparable. At the end of the light period, when aMT injections have an antigonadotropic effect, a peak of aMT synthesis was always present. Although MI synthesis showed seasonal rhythmicity, no reproductive cycle occurred in the hamsters. At present, the concept that the pro- and/or antigonadal effects of the pineal are mediated by aMT seems to be the most acceptable. The present results, however, indicate that aMT and perhaps other MI, often regarded as factors influencing gonadal growth in golden hamsters, are not the only factors involved.
    Materialart: Digitale Medien
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  • 10
    ISSN: 1435-1463
    Schlagwort(e): Pineal gland ; melatonin ; 5-methoxyindoles ; day/night rhythmicity ; reduced neopterin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary In the present study the effect was tested of reduced neopterin (RN) on the methylating capacity of the pineal gland of adult, male golden hamsters, housed under standardized conditions throughout the year. An effect of RN on the synthesis of a number of methylated compounds was, indeed, demonstrated. It is concluded that RN not only influences the indole metabolism by being the cofactor of tryptophan-hydroxylase, but that it might be involved in the regulation of other enzymes as well. Incubation with RN was most effective at the end of the light period. As this is also the time at which melatonin (aMT) injections cause gonadal atrophy in hamsters, kept under long photoperiod, this time of the day may be very important for aMT synthesis. A season-bound influence of RN was also demonstrated. The effect of RN was stimulatory in September, November and January for 5-methoxytryptamine (MT) and in November for 5-methoxytryptophan (MW) synthesis, but inhibitory in July. Furthermore, the effect of RN was stimulating for 5-methoxyindole-3-acetic acid (MA) and aMT in September, while the influence in the other months tested was absent or slightly inhibiting. These results suggest that the influence of RN in the pineal may be regulatory to various enzymes of the indole metabolism.
    Materialart: Digitale Medien
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