Effects of parenteral pharmacological magnesium loading on insulin secretion in experimental thyrotoxicosis.

Thyrotoxicosis is characterised by decreased magnesium pool and also insulin resistance. The present study is evaluating the parameters of glucose metabolism under pharmacological magnesium loading in experimentally induced thyrotoxicosis, in rats. Insulin secretion was significantly increased in thyrotoxicosis compared to controls, expressing probably the status of insulin resistance due to thyroxine excess. After intraperitoneal magnesium infusion, plasma magnesium reached pharmacologically high concentrations and insulin secretion decreased significantly, but this decrease was not accompanied by alterations of glucose homeostasis. In controls, we also found a tendency towards the decrease of insulin secretion after magnesium loading, but it did not reach statistical significance. Thus, insulin secretion seems more sensitive to the inhibitory effects of magnesium overload in experimental thyrotoxicosis.

Effect of thyroid hormones on osteolysis "in vitro".

The effect of triiodothyronine and thyroxine no the stimulation of the release of 45Ca was followed up in rat calvaria incubated "in vitro" and compared with the effect produced by parathormone. Both triiodothyronine and thyroxine stimulated osteolysis. The response was dependent on dose. Triiodothyronine may intensify the effect of parathormone if added to the incubation medium, whereas thyroxine does not exert the same effect. The results obtained demonstrated a well defined osteolytic effect of both thyroid hormones.

Effect of "APUD"-type hormones on osteolysis in vitro.

Besides their well-known actions, glucagon, ACTH, pentagastrin and insulin from the APUD series exert a direct action on the bone calcium content. Incubation with these substances of rat calvaria in vitro yields an evident stimulation of osteolysis with ACTH. Pentagastrin inhibits osteolysis. Glucagon and insulin inhibit parathormone-stimulated osteolysis, with no influence on the spontaneous one. Glucagon, resembling calcitonin, stimulates the 45Ca uptake from the incubation medium. The action of these substances completes the series of hormones influencing bone calcium metabolism, underlining possible interference actions of APUD-type hormones.

Effect of magnesium ion upon the calcitonin content of rat thyroid.

Thyroid calcitonin level was assayed in male rats after administration of magnesium gluconolactate. The resulting acute hypermagnesemia caused a significant decrease in calcitonin. However, calcemia showed unimportant changes, which suggests that the inhibitory action of magnesium is exerted directly on calcitonin secretion and is not affected by the calcium ion.

Blood levels of some electrolytes and hormones during exercise in athletes.

Athletes (8 trained medium and long distance runners) have been explored before and after physical exercise under two testing procedures. After the ergometric test significant increases of Ca++ and Mg++ in serum and significant decrease of Mg++ in erythrocytes occurred. A marked increment of the cortisol level and lesser changes of the thyroid hormones have been found. After the specific training program, apart from the significant reduction of the erythrocyte Mg++, a very significant increase of the cortisol level and large increments of T3 occurred. All subjects showed good coping resources, with inter-individual differences for other three psychological variables.

Insulin secretion in magnesium silicate-induced osteopenia in rats.

Local inflammation induced in rats by subcutaneous injection of magnesium silicate is followed by general metabolic, endocrine and immune reactions. Three weeks after inflammation induction, important bone loss, inflammation-mediated osteopenia (IMO) were found. The study proposes to investigate if IMO influences endogenous insulin secretion and if insulin therapy modifies the amount of bone loss, knowing its osteoprotective effect. Experiments were carried out on adult rats, three weeks after local inflammation induction. Baseline glucose and insulin levels did not change as compared to controls. After glucose stimulation, insulinogenic index decreased in the IMO group, which evidences decrease of insulin secretion. Insulin treatment initiated at the same time with IMO did not induce significant changes as regards the response to glucose tolerance test. However, bone calcium was increased as compared to the untreated IMO group, without reaching the control level.

Changes in calcitonin secretion and in serum magnesium following adrenalectomy in rats.

The level of serum magnesium and also thyroid of calcitonin content was followed up in the conditions of adrenalectomy after hydrocortisone replacement as well as after calcium propranolol administration. Six days after adrenalectomy a significant decrease both of calcitonin secretion and of serum magnesium was noted. Hydrocortisone replacement reestablished the levels of both parameters to the levels found in controls. Adrenalectomy also reduced the calcitonin secretory response consequent to calcium loading, but calcium excess simultaneously determined hypermagnesemia. Propranolol, a beta blocker with direct action on the secretory tonus of the thyroid C cells, completely annulled the stimulation effect of calcium in adrenalectomized animals but not the hypermagnesemic response. The adrenocortical hormones interfere in the calcitonin-magnesium secretory antagonism, together with the sympathetic -adrenergic system, ensuring the secretory control of calcitonin especially by blocking the occurrence of an excess of magnesium which reduces calcitonin secretion.

Stimulating effect of calcium channel activator BAY-K 8644 on calcitonin secretion.

The calcium channel activator BAY-K 8644 injected intravenously produces a significant rise in the calcitonin content of the thyroid. Because adrenalin and noradrenaline play a certain role in the regulation of ionic calcium channels and in the preservation of the secretory tonus of the calcitonin secreting C cells, the effect of BAY-K 8644 was followed-up in adrenalectomized animals and in animals in which propranolol was previously administered. Adrenalectomy of beta receptor blocking does not prevent the effect of BAY-K 8644 on the activation of calcium channels, the calcitonin secretion being stimulated in these conditions too. The data obtained stress the relative independence of the calcium channels or the beta-adrenergic stimulating system in the achievement of calcium ion transfer. However, the calcitonin levels obtained were lower in adrenalectomized animals or following propranolol after stimulation with BAY-K 8644 in those with intact sympatho-adrenergic tonus. This stresses the importance of the integrity of the beta receptors in the activation of the calcium channels.

Effect of calcitonin on phosphorylase a and glucose-6-phosphatase activities in the hepatic particulate glycogen of rats.

A single dose of calcitonin (CT) (70 mU MRC/100 g body weight) was administered in 50 and 90 days old male Wistar rats. In both ages CT determined a rise of Phosphorylase a and glucose-6-phosphatase activity as well as an increased calcium accumulation at the level of liver particulate glycogen. In the rats receiving CT glycemia increased and the liver glycogen content decreased. With the exception of liver glycogen the other metabolic parameters studied were modified at the two ages in the same manner under the influence of the same dose of CT.

Inhibitory role of somatostatin on calcitonin secretion.

Calcitonin (CT) secretion is not exclusively controlled by calcemia, but the secretory tonus is maintained by the beta-stimulatory adrenergic system Somatostatin (SMS) plays a neuromodulatory role with the reduction of CT secretion by its interference at the central and peripheral level of the beta adrenergic receptors. The experiments were carried out on groups of rats in which the effect of SMS on CT content of the thyroid gland was followed up. Thus, SMS administered i.c.v. significantly reduced the basal CT secretion without blocking the stimulatory effect of calcium. The results were comparable with those obtained after the blockade of the sympatho-adrenergic system by chemical sympathectomy with 6HODA or propranolol. Central blockade of alpha receptors with phentolamine determined a significant rise of CT. This effect was annihilated by SMS. The i.v. administration of SMS did not induce a change in CT content of the thyroid, but blocked the stimulatory action of hypercalcemia. The results are identical with those obtained by blocking the beta-receptors with propranolol. SMS also blocked the stimulatory effects of isoproterenol on CT secretion. The data obtained revealed the fact that SMS lowers CT secretion by the central and peripheral interference of the sympatho-adrenergic path, maintaining the secretory tonus of the thyroid C cells.

Calcitonin secretion in rats with inflammation mediated osteopenia.

The authors followed up the occurrence of inflammation-mediated osteopenia (IMO) in young and adult rats weighing 50 g and 150 g, respectively. The calcemia, the amount of bone calcium and the calcitonin content of the thyroid gland were determined. Calcium loss from bones was similar in both groups, irrespective of age. However, in the young animals a significant rise of calcitonin content of the thyroid gland was found (11.08 ng/ml as compared with 3.81 ng/ml in the controls). In adult animals with IMO the level of calcitonin in the thyroid gland showed no change as compared with the controls. Calcitonin reactive hypersecretion in the young animals was not able to prevent the development of IMO, characterized by an important loss of bone calcium.

The mechanism involved in the central effect of 5-leu enkephalin on the calcitonin secretion.

Calcitonin (CT) secretion is not exclusively under the control of calcium levels in the plasma, but also depends on the sympathetic-adrenergic tone. In previous experiments we stressed out the possible role played by 5-leu enkephalin (5-LE) in the nervous regulation of the CT secretion. Intracerebroventricular (i.c.v.) 5-LE in doses of 100 micrograms could act at a central level through a mechanism independent from the noradrenergic pathways, since i.c.v. 6-OHDA and propranolol could not interfere with its stimulatory effect on the CT content of the thyroid. In the present experiments, performed in anaesthetized Wistar-Bratislava rats, we studied the involvement of mu and delta receptors in the central effect of 5-LE on the CT content of the thyroids and the CT levels in the plasma. These parameters were measured in parallel, by means of a competitive radioimmunoassay with double antibodies (Peninsula Lab.). 5-LE probably bound to both mu and delta receptors, since its effect on the CT secretion was reversed by 13 micrograms of naloxone (i.c.v.). A partial blockade, comparable to naloxone, was noticed after 382 micrograms of CTOP (i.c.v.), a specific antagonist of the mu receptors--stressing out their involvement in the stimulatory effect of 5-LE on the CT secretion. 250 Ug of ICI 174864 (i.c.v.), a selective antagonist the the delta receptors completely blocked the stimulation induced by 5-LE on the CT secretion to values significantly lower as compared to the controls and even to the sympathectomized group. This suggests the tonic role played by enkephalins in the CT secretion, through the central activation of delta receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum cholinesterase activity correlates with serum insulin, C-peptide and free fatty acids levels in patients with type 2 diabetes.

When compared with values recorded in 14 control subjects, the 15 overweight patients with type 2 diabetes displayed significantly increased activities of serum alanineaminotransferase (172% of mean values in controls), gamma-glutamyltransferase (253%) and cholinesterase (139%). A much wider dispersion of individual values for the two firstly mentioned enzymes was however noted so that their correlation with serum triglycerides levels were weaker (r = 0.373; p < 0.05 and r = 0.451; p < 0.05 respectively) than the same correlation obtained for serum cholinesterase (r = 0.760; p < 0.001). In two other studies including 28 controls and 30 diabetic patients serum cholinesterase was found to be significantly correlated with serum levels of insulin (r = 0.622; p < 0.001), C-peptide (r = 0.652; p < 0.001) and free fatty acid (r = 0.821; p < 0.001). Circumstantial evidence is provided that insulin resistance and an increased flux of free fatty acids from adipose tissue to the liver would stimulate the hepatic synthesis of serum cholinesterase.

The role of some activators and inhibitors of calcium channels on the dynamics of serum magnesium.

Magnesemia was determined in male rats weighting 120 +/- 10 g after intravenous administration of nifedipine, an antagonist of calcium channels, and BAY-K 8644, an activator of calcium channels. Nifedipine does not alter the basal level of serum Mg 30 minutes after administration in normal animals or in animals in which chemical sympathectomy was induced by administration of 6 OH-dopamine. On the other hand, BAY-K 8644 induces a significant rise of basal magnesemia from 2.1 +/- 0.2 mg% to 2.7 +/- 0.1 mg% in normal animals. In animals sympathectomized with 6 OH-dopamine, their rise is maintained at about the same level from 2.0 +/- 0.1 mg% after administration). Propranolol previously administered inhibits the stimulating action induced by the calcium channel agonist, BAY-K 8644.

The effects of the intraperitoneal administration of midazolam on blood glucose level and serum lipids in streptozotocin-induced diabetes in rats.

In male Wistar rats rendered diabetic by streptozotocin administration, the intraperitoneal (i.p.) injection of midazolam (2.5-5.0 and 10 mg/kg) induced a significant reduction of hyperglycemia and hyperlipidemia. The plasma immunoreactive insulin level was slightly, but significantly increased. The lethality was diminished.

The effect of some enkephalins on calcitonin secretion.

Synthetic enkephalins: 5 metenkephalin, D2 proenkephalin and 5 leuenkephalin and morphine were injected into cerebral ventricles of rats. After 30 minutes the rats were sacrificed and the calcitonin content of the thyroid was assayed. As compared to the controls, morphine reduced significantly the secretion of calcitonin. Of the enkephalins, only 5 leuenkephalin had a borderline effect on calcitonin secretion, stimulating to a significant degree the rise of the hormone. The data obtained demonstrate the selective effect of opiates on calcitonin secretion.

Stimulation of calcitonin secretion by beta-calcitonin gene related peptide in rats.

The presence of calcitonin gene-related peptide (CGRP) in both C-cells and nerve fibres around the thyroid blood vessels and follicles suggests that it may play a dual role, one of which may be in hormone secretion. Beta-CGRP injected intracerebroventricularly (icv) (1.875 nmol) caused a significant increase in the calcitonin CT) content of the C-cells in rat thyroid glands. The calcitonin content of the thyroids was determined by a radioimmunoassay using two antibodies and the results were expressed as ng CT/mg of fetal tissue. A significant rise in CT content of the thyroids occurred (5.5 +/- 0.5 n = 6), compared with the controls (3.5 +/- 0.1 n = 6). It is presumed that this change reflects an increase in the rate of secretion of CT in the thyroid glands of those rats so treated. The peptide might act on the central nervous system to stimulate the catecholamine outflow from the thyroid nerves and thereby increase the secretion rate of CT.