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  • glucagon  (5)
  • indoles  (4)
  • 1
    ISSN: 1432-0428
    Keywords: Metabolic control ; artificial pancreas ; lactate ; pyruvate ; glycerol ; non-esterified fatty acids ; total ketone bodies ; glucose turnover ; glucose recycling ; glucagon ; growth hormone ; Type 1 diabetes ; subcutaneous insulin therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twelve insulin deficient Type 1 (insulin-dependent) diabetic subjects were studied over an 11 1/2 h period during both subcutaneous insulin therapy and closed loop insulin delivery, using a glucose controlled insulin infusion system (Biostator) programmed to maintain normoglycaemia. Results were compared with those from 21 age and weight-matched normal subjects. Using the Biostator, normoglycaemia was achieved in all diabetic subjects within 3.5 h and normal profiles maintained thereafter. Blood metabolite and hormone values were evaluated during the subsequent 8 h normoglycaemic period. Subcutaneous therapy resulted in abnormal glucose levels throughout the study period (mean 8 h value 8.3±0.7 compared with 5.6±0.3 mmol/l on feedback control and 5.5.±0.1 mmol/l in normal subjects). The mean value of lactate and pyruvate over the final 8 h period was 25% higher in diabetic patients than in normal subjects with no difference between the two insulin treatments (blood lactate: 0.94±0.04 on subcutaneous insulin, 0.91±0.04 on feedback control and 0.74±0.03 mmol/l in control subjects). The pre-prandial peaks of blood glycerol and plasma non-esterified fatty acids were significantly decreased or absent during both feedback control and subcutaneous therapy in comparison with the normal subjects, whereas after the midday and evening meals, total ketone body levels were significantly higher in the diabetic patients. Peripheral serum free insulin levels were two-to fourfold greater in the diabetic than in the normal subjects. There were no significant differences between levels in diabetic patients receiving subcutaneous insulin or on the Biostator. Glucose turnover (1600–1800 h) was normal on feedback control (1.41±0.20 versus 1.55±0.18 mg · kg-1 · min-1 in the normal subjects) but was significantly decreased during subcutaneous insulin (1.04±0.09 mg · kg-1 · min-1). There was, in addition, a decrease in glucose recycling during both subcutaneous insulin therapy and feedback control in the diabetic subjects. These data suggest that although fine control of glucose metabolism both in terms of circulating concentrations and rates of production can be achieved by feedback-control, insulin infusion by the peripheral route is associated with significant metabolic abnormalities, at least in the short term. Longer term studies and examination of portal insulin delivery seem warranted.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Artificial endocrine pancreas ; glucose clamping ; hyperglycaemia ; insulin-dependent diabetes ; blood glucose ; ketone bodies ; alanine ; lactate ; pyruvate ; ketogenesis ; insulin ; glucagon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The metabolic and hormonal effects of stable hyperglycaemia (10–12 mmol/l) have been examined in five insulin-dependent diabetics and compared with the results of 8 h (1200 to 2000 h) normoglycaemic (5–6 mmol/l) clamping. Glucose levels were maintained using a glucose controlled insulin infusion system. Mean blood lactate, pyruvate, total ketone bodies, glycerol and plasma nonesterified fatty acids were similar during the period of stable glycaemia at the two glucose levels. In contrast mean blood alanine was markedly elevated during hyperglycaemic clamping (0.384 ± 0.008 vs 0.298 ± 0.021 mmol/l) and 3-hydroxybutyrate was slightly decreased (0.068 ± 0.007 vs 0.084 ± 0.008 mmol/l). Plasma glucagon levels were raised during hyperglycaemic clamping and growth hormone slightly decreased. There was a close positive correlation between mean blood alanine and mean blood glucose (r = 0.79, p 〈 0.01), and a negative correlation of alanine with the amount of insulin infused (r =-0.72, p 〈 0.01). It is suggested that the raised alanine results from increased peripheral glucose utilisation. In general a short period of stable hyperglycaemia is not associated with a worsening of metabolic abnormalities in insulin-dependent diabetic subjects.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Insulin ; glucagon ; secretin ; vaso-active intestinal polypeptide ; glucose ; glycerol and 3-hydroxy-butyrate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A comparison of the metabolic and gastroentero-pancreatic hormonal responses of ten obese and eight lean subjects to 12 h and 36 h fasts has been made. Each subject was given a 50 g oral glucose tolerance test at the end of both 12 h and 36 h starvation. After the 12 h fast blood glucose and 3-hydroxybutyrate were similar in each group but blood glycerol was 30% higher in the obese subjects. Plasma insulin and vaso-active intestinal polypeptide were also higher in the obese subjects after 12 h starvation. After 36 h starvation in the lean subjects blood glucose was unchanged but on refeeding with 50 g oral glucose, glucose tolerance was impaired. In the same group blood glycerol and 3-hydroxybutyrate rose after 36 h starvation. Plasma glucagon, secretin and vaso-active intestinal polypeptide rose after 36 h starvation in the lean subjects but plasma insulin was unchanged. Refeeding with oral glucose suppressed the increased plasma glucagon, secretin and vaso-active intestinal polypeptide. After the 36 h fast in the obese subjects, blood glucose was unchanged, blood glycerol fell, but blood 3-hydroxybutyrate rose although to a reduced level in comparison with the lean subjects. In the obese group there was no change in plasma glucagon, secretin or vaso-active intestinal polypeptide after 36 h starvation, although plasma insulin fell. The results show different metabolic and gastro-entero-pancreatic hormonal responses to fasting in lean and obese human subjects and suggest an important metabolic role of glucagon, secretin and vaso-active intestinal polypeptide during starvation.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Growth hormone ; insulin ; insulin deficiency ; glucagon ; blood glucose ; ketone bodies ; ketogenesis ; lipolysis ; non-esterified fatty acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 23-28 
    ISSN: 1432-1041
    Keywords: dopamine ; somatostatin ; insulin ; glucagon ; growth hormone ; plasma glucose ; NEFA ; lipolysis ; ketogenesis ; insulin-deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1435-1463
    Keywords: Pineal gland ; continuous light ; ovulation ; indoles ; melatonin ; HIOMT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1435-1463
    Keywords: Pineal ; indoles ; gonads ; chick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 33 (1972), S. 179-194 
    ISSN: 1435-1463
    Keywords: Pineal ; indoles ; gonads
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 34 (1973), S. 49-60 
    ISSN: 1435-1463
    Keywords: Pineal ; indoles ; gonads ; chick
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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