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  • lipolysis  (5)
  • indoles  (4)
  • 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 gland ; continuous light ; ovulation ; indoles ; melatonin ; HIOMT
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The aim of the present study was to investigate whether the ovulation-maintaining effect of melatonin in rats, exposed to continuous light (LL), was also exerted by other pineal indoles which have been reported to influence the reproductive processes of mammals. The effect of 10μg melatonin was compared with that of similar amounts of either N-acetylserotonin, 5-methoxytryptophol, 5-methoxyindole-3-acetic acid, 5-hydroxytryptophol, 5-methoxytryptamine or 5-methoxytryptophan. All these compounds appeared to be significantly less effective than melatonin in preventing the effect of LL, ovulation being preserved in only 20–33 % of the rats investigated, with melatonin this percentage being 60–75%. Investigations were also carried out to assess the effect of these indole derivatives on HIOMT (hydroxyindole-O-methyl transferase) activity in synthesizing different 5-methoxyindoles in the abnormally influenced pineal gland due to LL. Melatonin, the compound the effect of which on ovarian cyclicity is strongest, stimulates 5-methoxytryptophol synthesis; while other less active compounds stimulate the synthesis of melatonin and inhibit that of O-acetyl-5-methoxytryptophol. The possibility that the effect of other indoles than melatonin on ovarian cyclicity might be due to stimulation of melatonin synthesis was considered. A possible functional relationship of the different indoles cannot be excluded.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neural transmission 34 (1973), S. 159-169 
    ISSN: 1435-1463
    Schlagwort(e): Pineal ; indoles ; gonads ; chick
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Identical age, body weight, or initial comb size are not useful as parameters in analysing effects of pineal substances on the gonadal system of adult white leghorn hens. A combination, however, of the initial comb size with the frequency of oviposition proved to be an adequate parameter. Administration of 5-methoxytryptophol in increasing concentrations to adult hens shows an inhibitory effect on ovarian and follicular weight. This effect is not only realized by a decrease in organ weight, but also by a retardation of the rhythm as expressed in initial comb size units. As follicular growth is mainly dependent on a FSH/LH ratio in which the LH content is increased, the inhibitory effect may possibly be described to this relation.
    Materialart: Digitale Medien
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neural transmission 33 (1972), S. 179-194 
    ISSN: 1435-1463
    Schlagwort(e): Pineal ; indoles ; gonads
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Testes weights of white leghorns of the same age or of equal body weight vary considerably. Experiments on the effects of pinealectomy, administration of pineal extracts or indolic compounds on the testes weights therefore require better parameters. Cockerels having a similar initial comb size prove to have testes of similar weights. Experiments using this parameter permit a more exact comparison of control and experimental animals. Administration of 5-methoxytryptophol and melatonin in increasing concentrations to juvenile, maturing and adult white leghorn males shows an age-dependent activity. In juvenile birds, the testes and comb growth are stimulated by 5-methoxytryptophol and melatonin, whereas in maturing and adult cocks both indolic compounds show an inhibitory effect. It appears that the effect of 5-methoxytryptophol is more specific than that of melatonin in juvenile as well as in maturing and adult white leghorns.
    Materialart: Digitale Medien
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    Journal of neural transmission 34 (1973), S. 49-60 
    ISSN: 1435-1463
    Schlagwort(e): Pineal ; indoles ; gonads ; chick
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Concerning the gonads, the initial comb size in white leghorn cockerels proved to be a parameter which permits a more exact comparison of control and experimental animals, than the generally used parameters of identical age and/or body weight. As in literature contradictory results are described after injecting different concentrations of 5-methoxyindoles, it may be possible that these results can be explained by the parameters used. To analyse this, several concentrations of 5-methoxytryptophol were injected in increasing amounts in white leghorn cockerels, using the comb size as a parameter. In all experiments a stimulatory effect of 5-methoxytryptophol on testicular weight was observed. Administration of the smallest concentrations (0.1–3.5μg, exp. I, and 1.0–35μg, exp. II) showed an acceleration of the growing rhythm of the testes if compared with the control animals. With the comb size as a parameter it was possible to analyse the degree of stimulation in comb size units. Administration of 2.5–87.5μg (exp. III) and of 10–350μg (exp. IV) of 5-methoxytryptophol resulted also in a stimulatory activity on testicular growth; acceleration of the growing rhythm, however, now proved to be irregular and could not be compared with the growing pattern of the testes in the control animals.
    Materialart: Digitale Medien
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