Different modes of activating phosphofructokinase, a key regulatory enzyme of glycolysis, in working vertebrate muscle

Glycolytic flux in white muscle can be increased several-hundredfold by exercise. Phosphofructokinase (PFK; EC 2.7.1.11) is a key, regulatory enzyme of glycolysis, but how its activity in muscle is controlled is not fully, understood. In order not to neglect integrative aspects of metabolic regulation, we have studied in frogs (Rana temporaria) a physiological form of muscle work (swimming) that can be triggered like a reflex. We analysed swimming to fatigue in well rested frogs, recovery from exercise, and repeated exercise after 2 h of recovery. At various times, gastrocnemius muscles were tested for glycolytic intermediates and effectors of PFK. All metabolites responded similarly to the…

Eye Muscle Antibodies in Endocrine Exophthalmos

Serum samples were obtained from 65 patients with endocrine exophthalmos class I-V. In 33/65 patients who were treated either with prednisone or with ciclosporin, blood was sampled before, during and after therapy. Antibodies against eye muscle were determined during the course of immunosuppressive therapy in order to have an objective parameter of the therapeutic effect. To ascertain the specificity of the reaction both eye and abdominal muscles were used as antigens in an ELISA system. Both IgG and IgM antibodies were detected. In 45/65 patients (71%) eye muscle antibodies were positive before starting therapy. Antibodies were mostly detected in patients with active disease. Patients with…

Die Messung des freien Speichel-Cortisols vor und nach intravenöser Stimulation mit Corticotropin-Releasing Hormon. Der Einfluß basaler Cortisolspiegel auf die Stimulierbarkeit.

Spermiogrammbefunde bei männlichen Patienten nach Alkoholdelir

Zusammenfassung Bei 30 Patienten mit alkoholtoxischem Delir wurden die wichtigsten Spermiogramm-Parameter untersucht: Es wurden bei verminderter Spermatozoendichte von im Mittel 18 Mill.Sp./ml gehauft eine Hypospermie (n = 8) beobachtet. Beurteilt man Spermatozoendichte, Morphologie und Motilitat, so erweisen sich 29 der 30 Untersuchten Spermiogramme als stark pathologisch verandert. Die Spermiogenese-Storung ist bei erhohter FSH-Basiswerten (n = 10) und bei akuter alkoholtoxischer Hepatitis (n = 4) am ausgepragtesten (2a = 0.01), hangt dagegen weniger vom Trinkerstadium nach Jellinek, erhohten Ostradiol-Werten (n = 6) oder erhohten CK-Werten (n = 8) ab. Bei Alkoholkranken bei offensichtlic…

Exercise and recovery in frog muscle: metabolism of PCr, adenine nucleotides, and related compounds

The effects of exercise (swimming), fatigue, and recovery on the intracellular pH (pHi), energy-rich phosphates, and related metabolites were studied in the gastrocnemius muscle of common frogs (Rana temporaria) at 20 degrees C. Exercise caused a rapid decrease in the content of phosphocreatine (PCr) and a corresponding increase in that of Pi. The ATP level remained virtually constant for 1 min; its precipitous decrease during the following minute was associated with a rise in the contents of inosine 5'-monophosphate (IMP) and NH4+, indicating a marked activation of AMP deaminase. Five minutes of swimming caused severe fatigue, which was correlated with decreases in muscle PCr (-85%), ATP …

Thyrotropin-releasing hormone has stimulatory effects on ventilation in humans

Thyrotropin-releasing hormone (TRH) stimulates pituitary thyrotropin synthesis and release and also regulates autonomic nervous system functions by acting as a neuromodulator and neurotransmitter. In experimental animals a stimulation of ventilation by thyrotropin-releasing hormone was shown when applied at central nervous system sites that affect respiratory motor output. It was the goal of our study to investigate the respiratory properties of thyrotropin-releasing hormone on basal and stimulated (i.e. CO2-rebreathing) conditions following systemic thyrotropin-releasing hormone application in healthy humans. Thyrotropin-releasing hormone (200 micrograms, 400 micrograms intravenous) initia…

Control of glycolysis in vertebrate skeletal muscle during exercise

The gastrocnemius muscle of the frog (Rana temporaria) has a high capacity for anaerobic glycolysis from glycogen. Glycolytic metabolites and effectors of phosphofructokinase, particularly the hexose bisphosphates, were followed in muscle during exercise (swimming between 5 s and 5 min), recovery (rest for up to 2 h after 5 min of swimming), and repeated exercise (swimming for up to 60 s after 2 h of recovery). Glycogen phosphorylase and phosphofructokinase were swiftly activated with exercise. The hexose bisphosphates followed markedly different time courses. Fructose 1,6-bisphosphate was transiently increased in both exercise and repeated exercise. This appears to be an effect rather tha…

Urinary glycosaminoglycans in Graves' ophthalmopathy.

An increased accumulation of glycosaminoglycans (GAG) in retrobulbar tissues has been reported in patients with thyroid eye disease. We examined the quantitative urinary GAG excretion in 101 patients with Graves' ophthalmopathy of different classes, 36 patients with Graves' hyperthyroidism without ophthalmopathy, 14 patients with toxic nodular goitre and 103 control subjects. Glycosaminoglycans were isolated from 24-h urine collections by precipitation with cetylpyridinium chloride and ethanol followed by photometrical quantification of hexuronic acids after reaction with carbazole. In comparison with the control group (15.8, 10.4, 21.6 mg/24 h; median, 25th, 75th percentile) a significant …

The effects of equal caloric amounts of xylitol, sucrose and starch on insulin requirements and blood glucose levels in insulin-dependent diabetics

Xylitol has been suggested as a potentially useful sweetener in the diabetic diet. In 14 insulin-dependent diabetics a standard diabetic diet regimen was compared with diets in which starch was isocalorically exchanged in the breakfast meal by either 30 g xylitol or 30 g sucrose. Insulin requirement and blood glucose were measured using a glucose-controlled insulin infusion system. The results following breakfast with xylitol were similar to those after starch breakfasts. Sucrose, in contrast, induced a greater post-prandial rise in blood glucose levels despite counter-regulation by the glucose-controlled insulin infusion system. Insulin requirement after sucrose significantly exceeded (p l…

Hypophysäre/Ovarielle Wirkstoffe

Ciclosporin and thyroid-stimulating immunoglobulins in endocrine orbitopathy.

The study investigated whether ciclosporin (C) affected the thyroid-stimulating immunoglobulins (TSI) in serum of patients with endocrine orbitopathy (EO). The effect of C was compared with that of prednisone (P). Fifteen patients with EO classes III-V received C (n = 7) or P (n = 8). In addition to the immunosuppressants, five patients with Graves' disease in each group received methimazole (MMI). The stimulation of the cAMP levels in the medium of thyrocyte cultures was determined as a parameter of TSI. The TSI levels were markedly lowered in both groups during and after therapy. C group: before therapy 6.2 pmol/ml +/- 1.63 (100%, mean +/- SEM), during treatment 4.6 pmol/ml +/- 2.28 (74%)…

A CRF-Producing and -Secreting Tumor of the Lung

Corticotropin-releasing factor (CRF) has recently been isolated from ovine hypothalamus, characterized chemically, and synthesized. Upton and Amatruda (1971) first suggested that CRF-like activity occurred in neoplastic tissues, and Hashimoto et al. (1980) subsequently detected CRF-like activity in an extract of an ACTHproducing nephroblastoma. Recently, Carey et al. (1984) and Asa et al. (1984) used immunocytochemical techniques to demonstrate CRF in postmortem tumor material obtained from patients with a carcinoma of the prostate and an intrasellar gangliocytoma.

The influence of penbutolol and placebo on blood sugar levels and insulin consumption in the glucose-controlled insulin infusion system ("artificial endocrine pancreas").

The aim of the study was to investigate the influence of 40 mg of the beta-blocker penbutolol (Betapressin TM; Hoechst Ltd., Frankfurt/Main) in comparison to placebo on the insulin consumption on the blood sugar profile in twelve insulin-dependent diabetes (IDDM) patients. The patients were treated with penbutolol and placebo for a period of three days, and then were examined with the help of the glucose-controlled insulin infusion system. The blood sugar profile and insulin consumption over a 24 hour period was not affected by either penbutolol or placebo, nor could any changes be measured in these parameters when measured after food intake. After a submaximal exercise load on the bicycle …

Pavlovian conditioning of corticotropin-releasing factor-induced increase of blood pressure and corticosterone secretion in the rat

Corticotropin-releasing factor (CRF) is clearly involved in the central regulation of the pituitary-adrenal axis and, moreover, of autonomic nervous system functions. Enhanced sympathetic activity with subsequent increases in blood pressure and heart rate and attenuation of the baroreceptor reflex results from the intracerebroventricular (i.c.v.) administration of CRF. Additionally, the peptide has a variety of potent effects on behavioural responses in animals similar to those observed after an experimentally evoked stress. It was therefore of obvious interest to examine whether CRF is a possible mediator of the learning processes associated with physiological stress reaction patterns. Thi…

Long-term treatment of acromegaly with the somatostatin analogue SMS 201-995 over 6 months.

This study examined the effects of the long-acting selective mini somatostatin analogue (SMS) 201-995 in two acromegalic patients who were treated for 3 and 6 months, respectively. During treatment the mean growth hormone levels (25.3 and 20.8 ng/ml vs 5.9 and 10.6 ng/ml) and somatomedin C levels (6.2 and 6.2 IU/ml vs 3.3 and 3.8 IU/ml) decreased and the patients reported an improvement in their symptoms. The main side effect was an increase in stool fat excretion which did exceed the normal range (less than 7 g/day) in one patient. Five acromegalics who received 2 X 50 micrograms SMS 201-995/day for 5 days showed a significant increase of stool fat excretion (1.7 vs 3.5 g/day; p less than …

Effekt von Cimetidin und Promethazin auf die basale und histaminstimulierte Parathormonfreisetzung aus menschlichem Nebenschilddrüsengewebe in vitro

Cimetidin gewinnt in den letzten Jahren in der konservativen Behandlung des primaren und sekundaren Hyperparathyreoidismus (p, sHPT) ein zunehmendes Interesse, nachdem bei beiden Krankheitsbildern in mehreren klinischen Studien ein Abfall der Parathormonkonzentration (PTH) im peripheren Blut nachgewiesen wurde (2, 4). Obwohl auch gegenteilige klinische Berichte vorliegen (3), ergaben alle bisherigen in vitro Untersuchungen mit diesem H2-Receptorantagonisten an Nebenschilddrusenadenomgewebe gleichlautend eine Hemmung der basalen und histaminstimulierten PTH-Freisetzung (1, 6). Entsprechende Befunde konnten auch mit dem Histamin-H1-Receptor-Antagonisten Promethazin erhoben werden, so das Nebe…

Comparison of glycemic response and insulin requirements after mixed meals of equal carbohydrate content in healthy, type-1, and type-2 diabetic man

The postprandial insulin requirements after three mixed meals of equal carbohydrate and energy content were assessed in 10 type-1 and 12 type-2 diabetics by a glucose-controlled insulin infusion system. These were compared with the glycemic response to the same meals of 10 healthy individuals (glycemic index). In type-1 diabetics, we found the highest insulin requirements after consumption of a continental breakfast (low fibre, low protein, high fat). Ten percent less insulin was infused after milk (low fat, high protein) and 30% less after an English breakfast (high fibre, high protein). Type-2 diabetics showed no significant differences in insulin requirements between the three test meals…

Fine-needle biopsy of parathyroid adenomas

High-resolution real-time sonography was performed in 15 cases of clinically and chemically suspected primary hyperparathyroidism and in 20 patients with different thyroid nodules. The suspected enlarged parathyroid glands and the thyroid nodules were percutaneously punctured under sonographic control. Concentrations of parathyroid hormone, human thyroglobulin, and human calcitonin were measured in the aspirate, and immunocytology was performed. The mean concentration of the aspirated parathyroid hormone in the parathyroid glands was 4,013.6 pmol/l +/- 4,519 (SD) as compared with 14.9 pmol/l +/- 8.7 in the thyroid nodules. Thyroglobulin was present in the aspirated fluid of parathyroid aden…

Comparison of131I-metaiodobenzylguanidine scintigraphy with urinary and plasma catecholamine determinations in the diagnosis of pheochromocytoma

In a retrospective study of 31 patients with suspected pheochromocytoma we examined the preoperative results of 131I-metaiodobenzylguanidine (131-I-MIBG) scintigraphy and a fluorimetric urine catecholamine determination test. An additional radioenzymatic plasma catecholamine determination test was performed in 25 patients. In 14 of the 31 patients the diagnosis of pheochromocytoma was later histologically confirmed. In the remaining 17 patients the suspected diagnosis was finally rejected after a clinical decision had been made on the basis of clinical history, symptoms, laboratory and imaging tests. 131-I-MIBG scintigraphy apparently had a very high specificity (no false-positive results a…

Nachweis der verbesserten Kohlenhydrattoleranz bei juvenilen Diabetikern durch Ein-satz eines neuen Saccharase-Hemmers

Wir haben versucht mit Hilfe eines Glykosidhydrolasen-Inhibitors die Aufnahme von Kohlenhydraten zu vermindern und somit eine Glattung im Tagesprofil und eine Insulineinsparung zu erreichen. Dabei wurde untersucht, ob eine Verbesserung der Glukosetoleranz durch Verminderung der postprandialen Blutzuckerspritzen, Senkung der Nuchternblutzuckerwerte und geringeren Insulinverbrauch zu erreichen sei. Es wurden an der „kunstlichen B-Zelle“ zehn juvenile Diabetiker uber je 2mal 48 Std beobachtet. Die Patienten hielten wahrend des Behandlungszeitraumes ihre bisherige Insulin-Therapie und isokalorische Ernahrung bei. In randomisierter Reihenfolge bekamen durch 2–3 Wochen Placebo und dann eine gleic…

Intraoperative localization of malignant pheochromocytoma by 123-i-metaiodobenzylguanidine single probe measurement

Metaiodobenzylguanidine (MIBG) imaging is a well-established method for locating intra- and extraadrenal pheochromocytomas. We investigated whether preoperative injection of 123-I-MIBG might be useful for intraoperative staging of chromaffine tumor cells. This was performed in a 46-year-old patient in whom the diagnosis of a malignant pheochromocytoma had been established by 123-I-MIBG imaging and enhanced catecholamine secretion. The rationale for intraoperative staging in this patient was a discrepancy between computed tomography (CI) of the abdomen and the radionuclide imaging, because scintigraphy revealed a mass with MIBG uptake in the right lower abdomen that could not be visualized b…

Gonadotropinsekretion nach Stimulation mit einem hochwirksamen Analogon des Gonadotropin-Releasing-Hormon (GnRH) bei gesunden M�nnern

Potente langwirksame GnRH-Analoga sind von besonderem Interesse fur die Therapie des hypogonadotropen Hypogonadismus hypothalamischer Genese und des Kryptorchismus.

Effekt von Calcium und Magnesium auf die Parathormonfreisetzung aus humanem Parathyreoidea-Gewebe in vitro

The effects of calcium and magnesium on parathyroid hormone release from eight adenomas causing primary hyperparathyroidism and six hyperplastic glands causing hypercalcemic secondary hyperparathyroidism were investigated in vitro using single cell suspensions from the respective tissue. We observed suppression of parathyroid hormone release with increasing concentrations of either cation. The quantitative hormone secretions of both adenomatous and hyperplastic glands was identical.

Control of adenine nucleotide metabolism and glycolysis in vertebrate skeletal muscle during exercise.

The turnover of adenosine triphosphate (ATP) in vertebrate skeletal muscle can increase more than a hundredfold during high-intensity exercise, while the content of ATP in muscle may remain virtually unchanged. This requires that the rates of ATP hydrolysis and ATP synthesis are exactly balanced despite large fluctuations in reaction rates. ATP is regenerated initially at the expense of phosphocreatine (PCr) and then mainly through glycolysis from muscle glycogen. The increased ATP turnover in contracting muscle will cause an increase in the contents of adenosine diphosphate (ADP), adenosine monophosphate (AMP) and inorganic phosphate (P(i)), metabolites that are substrates and activators o…

An in vitro model for the study of human parathyroid gland tissue: Single cell suspensions and monolayer cultures

An in vitro model for studies of parathyroid physiology is described using single cell suspensions and adherent monolayer cultures of human parathyroid tissue. The isolated cells were viable and maintained functional properties tested by calcium and magnesium sensitivity. Parathyroid hormone (PTH) secretion could be suppressed by rising calcium and magnesium concentrations. The secretory behaviour of the cells was not altered by cultivation or cryopreservation. The morphological integrity of the individual cells after mechanical and enzymatic preparation was confirmed by light and electron microscopy.

LONG-ACTING AND SELECTIVE SUPPRESSION OF GROWTH HORMONE SECRETION BY SOMATOSTATIN ANALOGUE SMS 201-995 IN ACROMEGALY

In 6 of 7 acromegalic patients a single subcutaneous injection of 50 micrograms of a new octapeptide somatostatin analogue (SMS 201-995) reduced serum growth hormone (GH) from 30 +/- 12 ng/ml to 1.4 +/- 0.4 (mean +/- SEM). Serum GH remained below basal concentration for 9 h. In the remaining patient who had very high basal preprandial serum GH, SMS 201-995 produced a reduction in serum GH of only 20%. Plasma glucose concentrations were increased to the upper limits of the normal range when a high-carbohydrate meal was consumed 2 h after injection. In non-diabetic patients plasma glucose did not exceed 129 mg/dl. The 40% decrease in plasma glucagon, which lasted for 7 h after SMS 201-995 inj…

Respiratory Parameters after Systemic Corticotropin-Releasing Hormone Administration

Neuroanatomical studies on the distribution of corticotropin-releasing hormone (CRH) and its receptors (7) as well as physiological data suggest a regulatory function of endogenous CRH in hypothalamic and extrahypothalamic brain areas [1, 4]. Endogenous CRH acts within the endocrine hypothalamo-pituitary-adrenal axis and affects cardiovascular regulation and respiration through extrahypothalamic pathways. CRH also stimulates gluconeogenesis and release of plasma-catecholamines. Our experiments in humans also demonstrate an influence on respiration and on heart rate activity after systemic application of CRH. Respiratory parameters and heart rate were analyzed during steady-state conditions …

Safety and side effects of human and ovine corticotropin-releasing hormone administration in man.

Synthetic human and ovine corticotropin-releasing hormone (hCRH, oCRH) are commonly used as a diagnostic tool of the hypothalamo-pituitary-adrenal axis. In this paper reports about side effects after various modes of CRH-application are analyzed and compared to our corresponding data of human studies with hCRH and oCRH. Generally, CRH is well tolerated after single administration and interval-application of standard doses, although minor side effects appear sometimes after higher doses (greater than 200 micrograms hCRH, oCRH) of CRH-bolus-injections. Predominantly the cardiovascular system (e.g. tachycardia, hypotension, flushing) is affected; neuropsychological symptoms are only seen spora…

Radioimmunoassay of Plasma and Urinary Norepinephrine

Various analytical methods, such as fluorimetry, radioenzymic assay and in particular liquid chromatography are used for the analysis of norepinephrine (NA) in body fluids and tissue homogenates. These procedures, however, often lack sensitivity, are expensive and/or time consuming. Basing on our previous reports on the radioimmunoassay of chemically modified serotonin1, 5-hydroxy-3-indole acetic acid2 and normetanephrine (NMN)3, a sensitive radioimmunoassay of the N-acetyl,3-methoxy analogue of urinary and plasma norepinephrine was developed.

Treatment of Severe Reactive Hypoglycemia With a Somatostatin Analogue (SMS 201-995)

• Reactive (or postprandial) hypoglycemia can sometimes represent a severe disorder refractory to conventional therapeutic measures. We present in this first individual trial, to our knowledge, that the administration of a somatostatin analogue (SMS 201 -995) may alleviate the severity of complaints and does not appear to be diabetogenic. The effects of the somatostatin analogue were documented in a 5-hour oral glucose tolerance test, where not only the glucose-induced and C-peptide rise was clearly attenuated, but also the blood glucose concentration did not fall low enough to induce hypoglycemic symptoms. ( Arch Intern Med. 1990;150:2401-2402)

Knochenveränderungen bei Akromegalie

An 2 7 Frauen und 11 Mannern mit Akromegalie wurde die Knochendichte in Single-Photonenabsorptionstechnik am proximalen (uberwiegend Kompakta) und distalen (uberwiegend Spongiosa) Mespunkt des Unterarms untersucht. Die Knochendichte lag dabei am proximalen Mespunkt im zu erwartenden Altersnormbereich, am distalen Mespunkt war sie deutlich erhoht (p < 0,001). Die mit quantitativer Computertomographie gemessene Spongiosa der Lendenwirbelsaule fanden wir uber das Alter hinaus vermindert. Als Ausdruck eines gesteigerten Knochenabbaus fanden wir das Hydroxyprolin im Urin erhoht, wahrend sich das Osteocalcin als Marker der Osteoblastenaktivitat invers dazu verhielt.

Naloxone increases the response of growth hormone and prolactin to stimuli in obese humans.

Opiates stimulate the growth hormone and prolactin responses to stimuli in non-obese humans. Obese patients, however, show lowered growth hormone and prolactin responses and raised beta-endorphin levels. We therefore investigated the effect of the opiate antagonist naloxone on the stimulated growth hormone and prolactin secretions in a controlled double-blind study in obese patients. All patients received 200 micrograms TRH and 0.5 g/kg b.w. arginine together with 2 mg of naloxone or placebo i.v. in a randomized sequence. The TRH- and arginine-induced increases in prolactin and growth hormone were significantly greater after administration of naloxone (p less than 0.05). Naloxone also produ…