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  • 5-methoxyindoles  (6)
  • growth hormone  (4)
  • 1
    ISSN: 1432-0428
    Keywords: Phenformin ; sulphonylureas ; blood glucose ; lactate ; pyruvate ; ketone bodies ; alanine ; glycerol ; non-esterified fatty acids ; growth hormone ; gluconeogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twelve hour metabolic rhythms have been determined in two groups of subjects during combined therapy with a sulphonylurea and phenformin 50 mg twice daily. Subjects with clinical evidence of complications of diabetes showed greater abnormalities in concentrations of blood intermediary metabolites than a group of subjects without complications despite similar mean blood glucose concentrations in the two groups (7.6 mmol/l with complications; 7.3 mmol/l without complications). Mean blood lactate (1.93 mmol/l v 1.39 mmol/l), alanine (0.56 mmol/1 v 0.43 mmol/l), total blood ketone bodies (0.20 mmol/l v 0.14 mmol/l) and several other intermediary metabolites and their ratios were significantly higher in the group with diabetic complications. It is suggested that the differences between the two groups may arise from impaired disposal of phenformin leading to higher blood concentrations in the group with diabetic complications, despite normal liver function tests and plasma creatinine concentration. It is probable that this accumulation of phenformin results in more pronounced effect upon blood glucose and other intermediary metabolites. Thus, the metabolic abnormalities previously reported in patients treated by phenformin alone are also present during combined sulphonylurea and phenformin therapy, and in the presence of diabetic microangiopathy these abnormalities are accentuated.
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  • 2
    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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  • 3
    ISSN: 1432-0428
    Keywords: Phenformin ; metformin ; glibenclamide ; blood glucose ; lactate ; alanine ; pyruvate ; ketone bodies ; maturity-onset diabetes ; diabetic control ; gluconeogenesis ; glycerol ; insulin ; triglycerides ; growth hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twelve hour metabolic rhythms have been performed on six maturity-onset diabetic subjects during successive periods of therapy with phenformin, metformin, and glibenclamide. Moderate control of blood glucose concentration was achieved with phenformin and metformin, the lowest concentrations being found with glibenclamide. Mean blood lactate concentration was grossly elevated during phenformin therapy, moderately elevated with metformin and normal during glibenclamide treatment. Similar patterns were found for the lactate/pyruvate ratio, alanine, glycerol and ketone bodies. Serum triglyceride concentrations were significantly higher during phenformin treatment than with the other two regimes. Serum insulin concentration was higher on glibenclamide than with either biguanide. Most of these effects of the biguanides could be accounted for by an inhibitory effect on hepatic gluconeogenesis. It is concluded that the use of biguanides as hypoglycaemic agents in diabetes is associated with the production of multiple metabolic abnormalities.
    Type of Medium: Electronic Resource
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  • 4
    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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  • 5
    ISSN: 1435-1463
    Keywords: Pineal ; melatonin/5-methoxytryptophol ; 5-methoxyindoles ; pteridines ; red light
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1435-1463
    Keywords: Pineal ; melatonin/5-methoxytryptophol ; 5-methoxyindoles ; pteridines ; green light
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 7
    ISSN: 1435-1463
    Keywords: Pineal gland ; melatonin ; 5-methoxyindoles ; seasonal rhythmicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 8
    ISSN: 1435-1463
    Keywords: Pineal gland ; melatonin ; 5-methoxyindoles ; day/night rhythmicity ; reduced neopterin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
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  • 9
    ISSN: 1435-1463
    Keywords: Pineal gland ; 5-methoxyindoles ; photoperiod ; gonadal atrophy ; FSH ; LH
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Testes weight, plasma FSH and LH concentration and pineal methylating capacity were compared in hamsters housed under either long (LD 14∶10) or short (LD 8∶16) photoperiods. Hamsters housed for 14 weeks under short photoperiod showed gonadal atrophy, which was complete after 6 weeks. Also plasma FSH and LH concentration showed a marked decline after transfer to short photoperiod. However, after 14 weeks the concentration of FSH and LH as well as testes weight increased again. Under both photoperiods day/night rhythms in plasma FSH and LH concentration were measured. Under both light regimes the concentrations did not show significant differences. Under long as well as short photoperiods in the pineal gland of animals no significant differences were found in the daily synthesis of various MI tested. Only the synthesis of ML was significantly higher in the pineal of hamsters housed under short photoperiod. The function of this higher synthesis of ML remains unknown. Although the maxima of the rhythm for the various MI found under different LD regimes did not differ in magnitude or duration, their location in respect to the onset of darkness was different. It is suggested that this specific location is of more physiological importance than the quantity or duration of synthesis, concentration or release of MI. At the moment the day/night rhythms were determined there were indications that recrudescence of the testes had already started. It is suggested that this recrudescence is responsible for the fact that no differences in the synthesis of MI were found comparing the influence of both photoperiods. After 14 weeks of exposure to short photoperiod, aML synthesis was, in contrast to the synthesis of the other MI, (not significantly) higher under LD 8∶16. Moreover, opposite results for aMT and aML synthesis during darkness were found. It is suggested that the ratio of synthesis of these compounds is of physiological significance.
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  • 10
    ISSN: 1435-1463
    Keywords: Pineal gland ; HIOMT ; 5-methoxyindoles
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hydroxyindole-O-methyl transferase activity for the synthesis of 5-methoxyindoles was investigated in the pineal gland of 28 day old male Wistar rats after exposure to white, red and green light for 12 hours daily. It could be demonstrated that, in comparison to white light, red light causes a shift of HIOMT activity for the synthesis of melatonin/5-methoxytrypto-phol towards an earlier period being highest between 12 and 16 hours. The synthesis of 5-methoxytryptamine and of 5-methoxytryptophan is shifted to 16 hours, while the synthesis of 5-methoxyindole-3-acetic acid, which normally peaks at 16 hours, is increased at this same hour. Green light shifts HIOMT activity for the synthesis of melatonin/ 5-methoxytryptophol to a later period, showing a peak at 24 hours. The synthesis of 5-methoxytryptamine is significantly increased at 24 hours. An increase is also observed in the synthesis of 5-methoxyindole-3-acetic acid at 12 and at 4 hours, times at which this synthesis is also maximal using white light, whereas the synthesis of 5-methoxytryptophan is generally decreased. A possible relationship between the present results and those obtained after exposure to different wavelengths of light on N-acetyltransferase activity, the effect of pterins on HIOMT activity and the effect of different wavelengths on gonadal growth are discussed.
    Type of Medium: Electronic Resource
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