Changes of insulin binding in rat tissues after exposure to stress.

The effects of various stressors on insulin receptors in adipose, liver and skeletal muscle tissues were studied in rats exposed to acute or repeated stress. Adult male rats were exposed to immobilization (IMO) for 2.5 hours daily for 1, 7 and 42 days, or to hypokinesia (HK) for 1, 7 and 21 days. We determined the values of specific insulin binding (SIB) and insulin receptor binding capacity (IR) of plasma cell membranes from adipose, liver and muscle tissue (IMO groups), or insulin binding to isolated adipocytes and hepatocytes (HK groups). A significant decrease of SIB and IR was observed in rats exposed to acute stress (1x IMO) in muscle, adipose and liver tissues. However, in animals exposed to repeated stress (7x and 42x IMO), SIB and IR were diminished in the muscle tissue, whereas no significant changes were noted in the liver and adipose tissue. When tissue samples were collected 3-24 hours after exposure to IMO stress, no changes of SIB and IR were found in liver and adipose tissue, but insulin binding was lowered in skeletal muscles. In animals exposed to HK for one day, a decrease of SIB and IR was found in isolated adipocytes, but no changes in insulin binding were noted in the liver tissue. In rats exposed to HK for 7 and 21 days, values of IR were similar as in control group. Our results indicate a) the different changes of IR in the liver, fat and muscle tissues after exposure to stress situations, b) a long-term decrease of insulin binding in muscles of rats exposed to repeated IMO stress, and c) the return of reduced SIB and IR (induced by acute stress) to control values in the liver and adipose tissue after a short recovery period.     

Stress under normal conditions, hypokinesia simulating weightlessness, and during flights in space

Stress due to intensive mental work under normal conditions was compared to stress under a sharp limitation of motor activity (hypokinesia), simulating weightlessness on the human body. Mental stress causes typical alterations of cerebral circulation under normal conditions: increase of blood flow in the supramarginal and angular gyri of the parietal lobe, in the frontal lobe, and in the superior temporal gyrus of the left hemisphere, and changes in cardiac activity and in the tonus of vessels. Dynamics of human stress reactions, among other features of this process, is best reflected in the parameters of a electrocardiogram, a rheoencephalogram, and total peripheric vascular resistance. An increase in the latter is an informative index of stress development. Human reaction to stress under hypokinesia and during flights in space have specific features. Prolonged hypokinesia causes an imbalance in an organism's control systems, specifically depressor reactions are distorted. In the context of hypokinesia, anxiety and mental stress lose their adaptive nature to a large extent. They provoke disturbances of the heartbeat and hypertensive reactions. A whole complex of factors affects the living organism during space flights. An imbalance of the body's control systems, emotional and physical overloads, which arise episodically, changes in electrolyte and energetic metabolism, and alterations in the head vessels increase the probability of reactions to stress and reinforce their effect. Stress can be retarded by using on elaborated system of preventive measures which includes physical training, psychological support of astronauts and, to some degree, reduction of the hypothalamus adrenergic centers' tonus through muscle relaxation. Astronauts' reactions to being in space occur during flights under heavy loading tests and in emergency situations. Weightlessness does not generate stress when one has adapted to it. Returning from weightlessness to the Earth's gravitation causes stress. After prolonged flights, stress associated with readaptation to the Earth's gravitation is atypical in character (increase of sympatoadrenalic system activity against the background of a reduction in hypothalamo-hypophysial system activity). We explain the voltage decrease of the T-wave of the electrocardiogram, the phenomenon repeatedly occurring both during prolonged space flights and under hypokinesia, by a lowering of cardiomyocytes, energetic potential due to hypokalemia, insufficient glucose usage, and a decrease in the coupling of oxidative phosphorylation processes. [Translated from Fiziologiya Cheloveka, vol. 22, no. 2, 1996, p. 10-19]     

Tumor necrosis factor alpha in various tissues of insulin-resistant obese Koletsky rats: relations to insulin receptor characteristics.

Tumor necrosis factor alpha (TNFalpha) was found to be significantly increased in skeletal muscles and retroperitoneal fat of obese insulin-resistant Koletsky rats as compared to control Wistar rats. This increase was accompanied by a depression of insulin receptor protein tyrosine kinase (PTK) activity. Neither the insulin-binding capacity nor insulin receptor affinity were related to this TNFalpha increase in these tissues. In the liver, no significant changes of TNFalpha content and only a lowering of insulin-binding capacity were found. It is concluded that an increased TNFalpha content in muscles and fat (but not in the liver) contributes to insulin resistance by lowering insulin receptor protein tyrosine kinase activity, while other insulin receptor characteristics (insulin-binding capacity and affinity of insulin receptors to the hormone) do not seem to be influenced by this factor.     

Changes in the liver of albino rats after exposure to cold

The liver in the white rats subjected to the effect of a low temperature for 80 days (23 h every day, 5-7 degrees C) has been studied by means of a complex of morphometric techniques. The investigation is also performed 35 days and 4 months after the exposure to cold has been stopped. In the animals decapitated immediately after the exposure to cold has been stopped, there is a certain decrease in the liver mass, in the size of hepatocytes, drop in the karyometric indices. The latter phenomenon is also observed in the liver of the animals 35 days after the exposure to cold has been stopped. In 4 months, the part of the binuclear hepatocytes and the nuclear size is greater than in the control.     

Physical working capacity and factors responsible for it after exposure to 120-day antiorthostatic hypokinesia

The effect of 120-day antiorthostatic hypokinesia on human physical working capacity and functional state was studied. The study revealed two adaptation phases: the first phase is characterized by a significant decrease in working capacity and the second by relative readaptation. However, the unfavorable effect of 120-day antiorthostatic hypokinesia was evident as a decrease in the effectiveness of function of the cardiorespiratory system that increased the physiological cost of physical work.     

Changes in the lymph nodes of vaccinated rats after prenatal exposure to an antibiotic

Changes of anatomical structures and dynamics of cell composition have been studied in lymph nodes of one-month-old rats, vaccinated with typhoid vaccine and sexta-anatoxin, and of rats vaccinated in a similar way, but their mothers have been given tetracycline at early and late periods of pregnancy. After vaccination in 1, 3 and 7 days lymphocytic, blastic, macrophagal, plasmocytic; mast cells, neutrophilic and eosinophilic reactions have been observed in lymph nodes. In the offspring of the rats, that have been given tetracycline during preimplantation and implantation periods (the 1st-7th days of pregnancy) contents of small, middle lymphocytes, plasmocytes, macrophages, mast cells do not change. Neutrophilic and eosinophilic reactions are revealed only in medullary cords, that demonstrates certain inhibition of the immunological function. In the rats, whose mothers have been given tetracycline during embryogenesis (on the 15th-20th days of pregnancy) vaccination results in a considerable increase of the reactive state of the lymph nodes.     

Plasma trace elements concentrations in trained subjects after exposure to hypokinesia and daily hyperhydration

The objective of this investigation was to evaluate the effect of a daily intake of fluid and salt supplementation (FSS) on blood plasma trace elements concentrations in physically healthy volunteers after exposure to 364 d of hypokinesia (decreased number of steps per day). The studies were performed after exposure to 364 d of Hypokinesia (HK) on 30 long-distance runners of volunteers who had a VO₂ max 67 mL/kg/min and were ranging in the age of 19–24 yrs. Prior to their exposure to HK all volunteers were on an average of 10,000 steps/d. For the simulation of the hypokinetic effect the volunteers were kept under an average of 3000 steps/d. All volunteers were divided into three equal groups. The first group of volunteers subjected to HK and received daily FSS (water 26 mL/kg body wt and sodium chloride 0.16 g/kg body wt.), the second groups of volunteers submitted only to HK, and the third group of volunteers underwent a normal ambulatory life and served as control. The content of manganese, calcium, magnesium, iron, lead, copper, tin, nickel, zinc and cobalamine were determined in blood plasma of volunteers. By the end of the hypokinetic period the blood plasma concentration of microelements increased significantly in the hypokinetic subjects (second group), whereas in the hyperhydrated subjects (first group) decreased. It was concluded that prolonged restriction of motor activity induced significant increases in blood trace elements concentrations whereas daily hyperhydration had a normalizing effect on their concentration in blood plasma. This indicates that daily hyperhydration may be used to normalize blood plasma concentrations of microelements in physically healthy volunteers subjected to prolonged restriction of motor activity.     

Changes in insulin response to glucose after exercise training in partially pancreatectomized rats

The effects of exercise training on glucose-stimulated insulin secretion (GSIS) were studied in male Sprague-Dawley rats made mildly to severely diabetic by partial pancreatectomy. Exercise trained (10 wk treadmill; T) and untrained (Unt) rats were grouped according to posttraining fed-state hyperglycemia as follows: T less than 200 and Unt less than 200 (glucose concn less than 200 mg/dl), T 200-300 and Unt 200-300 (glucose concn 200-300 mg/dl), and T greater than 300 and Unt greater than 300 (glucose concn greater than 300 mg/dl). After exercise training, hyperglycemic glucose clamps were performed in awake rats by elevation of arterial blood glucose concentration 126 mg/dl above fasting basal levels for 90 min. Exercise training significantly increased muscle citrate synthase activity. Prevailing hyperglycemia was reduced during the 10-wk exercise training period in all T rats with fed-state glucose concentrations less than 300, and only 53% of Unt rats in these groups had reduced glycemia. GSIS was significantly higher in T less than 200 [2.4 +/- 0.7 (SD) ng/ml at 90 min] than in Unt less than 200 (1.5 +/- 0.3). A similar response was found for T 200-300 (1.1 +/- 0.3 ng/dl) vs. Unt 200-300 (0.7 +/- 0.1) but not T greater than 300 (0.36 +/- 0.2) vs Unt greater than 300 (0.44 +/- 0.05). Sham-operated control rats had insulin concentrations of 6.6 +/- 1.6 ng/ml at the 90th min of the clamp. Acute exercise reduced fed-state glycemia in rats with mild-to-moderate (less than 300 mg/dl) diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes of hydration of rats' tissues after in vivo exposure to 0.2 Tesla steady magnetic field

Hydration and [3H]ouabain uptake by different tissues of adult male rats were measured immediately after exposure to homogenous 0.2 T steady magnetic field. A time-dependent decrease of hydration and adaptation, followed by disadaptation, was detected in brain and liver tissues in most of the rats after 3.5-5 h of exposure. The number of functional active ouabain binding receptors, which correlates with cell volume, was also decreased in brain, liver, and spleen and increased in kidney tissue after half an hour of exposure. It is suggested that cell hydration is a second messenger through which the SMF exerts its influence.     

Changes in lipid ordering and state of aggregation in lymphocyte plasma membranes after exposure to mitogens

Summary An electron spin probe study was made of the effect of a number of mitogenic agents on the ordering and state of aggregation of the plasma membrane lipids of lymphocytes. These agents, which included phytohemagglutinin, Concanavalin A, the calcium ionophore A23187 and periodate, caused a 20% decrease in lipid ordering in the region of the bilayer probed by 5-nitroxide stearic acid. The corresponding methyl ester probe showed marked probe-probe interaction under the same conditions indicating an aggregation of lipids in the area probed by this label. Studies with mixed lipid vesicles and gangliosidefree cells indicate that these areas are rich in glycolipids capable of hydrogen bonding to the ester probe. The decrease in ordering and the increase in aggregation of the membrane lipids were correlated with the patching and capping of the ligand-receptor complexes. Furthermore, the disappearance of fluorescent ligand from the surface of treated cells corresponded with the return of the spectral parameters of the probes to control cell values.It was concluded that glycolipids might play an important role in ligand-induced cell surface changes either as bearers of receptor groups, as in the case of some gangliosides, or in association by hydrogen-bonding with receptor proteins.     

Effect of space flight factors on health of cosmonauts in the near and late term after space flights

Cytogenetical studies of cosmonauts' peripheral blood lymphocytes after space flights on MIR orbital station showed a statistically significant increase in the yields of radiation-induced chromosomal aberrations. However, similar studies with in vitro irradiation of biological objects with accelerated charged particles are of great importance for elucidation of the nature of cytogenetical damage induced in vivo. It is also important to investigate the structure of cosmonatus' diseases over their life, in particular, lens opacities and oncological diseases. Thus, the purpose of the investigations planned is to study cytogenetical damage in blood lymphocytes from cosmonauts after space flights on the ISS in vivo, as well as in donor blood lymphocytes after in vitro exposure to accelerated charged particles. The tasks of the project are as follows: determination of the yields and types of chromosomal aberrations in cosmonauts' blood lymphocytes before and after space flights, comparative studies of biological effects induced in vitro by different types of ionizing radiation in human blood lymphocytes in ground experiments, assessment of cytogenetical risks, analysis of the structure of cosmonatus' diseases comparing with that of whole population, study of the mortality and frequency of cataracts and oncological diseases in cosmonauts. The results to be obtained will be used for setting of health norms applied to the influence of radiations of different types, and for elaboration of measures to reduce health risks from space flight factors.     

Changes in innate forms of motor behavior in rats during long-term hypokinesia

The structure of motor behaviour in response to environmental tests--"open field" and "with-a-partner" situation (according to P. V. Simonov)--was studied in rats after 1, 3 and 6 weeks of hypokinesis, (to K. Hecht), as compared to the control. In control animals a relatively low level of orienting-investigation reactions and of grooming was observed as well as a low alimentary activity, which is considered as a manifestation of innate passive defensive reactions in the above situations. Disappearance of these reactions in the course of hypokinesia has two stages: predominant increase in orienting-investigating reactions (1-3 weeks); their subsequent decrease and an increase in the grooming (after 6 weeks). The relation between innate and conditioned behavioural changes is discussed as well as stability of alimentary behaviour in rats.     

Tryptophan force-feeding: Changes in the activities of acetylcholinesterase in various tissues of well-fed normal and adrenalectomized rats

The activity of acetylcholinesterase in the liver, heart, spleen, lungs and kidneys of well-fed normal and adrenalectomized rats was measured following a single tube-feeding of tryptophan. In well-fed normal rats, 30 min after tryptophan force-feeding, the enzyme activity in the heart and lungs was stimulated by 28 and 25% as compared to the water-fed control while in well-fed adrenalectomized rats acetylcholinesterase acticity in the heart, liver spleen and lungs was 40, 31, 22 and 15% increased, respectively over that of the corresponding control. In both groups of rats the enzyme activity in the kidney was unaffected by tryptophan. In the liver, spleen and heart of well-fed adrenalectomized rats the pattern of response for acetylcholinesterase to a tryptophan dose, over a period of 24-hr. was found to be biphasic. In well-fed adrenalectomized rats the tryptophan-mediated stimulation of acetylcholinesterase activity in the heart was found to be insensitive to actinomycin-D. The tryptophan-mediated stimulation of acetylcholinesterase activity in the heart of well-fed normal and adrenalectomized rats could not be related to the presence of an activator.     

Tocotrienol levels in various tissues of Sprague-Dawley rats after intragastric administration of tocotrienols

A tocotrienol (T3) mixture was intragastricaly administered to Sprague-Dawley rats, and the T3 levels in various tissues were measured 0, 4, 8 and 24 hr after the administration. In blood clots, brain, thymus, testes, vice-testes and muscles, T3 homologues were not detected at all. In epididymal adipose, renal adipose, subcutaneous adipose and brown adipose tissues and in the heart, the T3 levels were maintained or increased for 24 hr after the administration. In the serum, liver, mesenteric lymph node, spleen and lungs, the T3 levels were highest 8 hr after the T3 administration. These results suggest that the distribution and metabolism of T3 in the rat vary considerably among different tissues.     

Phosphate deposition during and after hypokinesia in phosphate supplemented and unsupplemented rats

The objective of this study was to show that prolonged restriction of motor activity (hypokinesia) could reduce phosphate (P) deposition and contribute to P loss with tissue P depletion. To this end, measurements were made of tissue P content, P absorption, plasma P levels, urinary and fecal P excretion of rats during and after hypokinesia (HK) and daily phosphate supplementation. Studies were conducted on male Wistar rats during a pre-hypokinetic period, a hypokinetic period and a post-hypokinetic period. All rats were equally divided into four groups: unsupplemented vivarium control rats (UVCR), unsupplemented hypokinetic rats (UHKR), supplemented vivarium control rats (SVCR) and supplemented hypokinetic rats (SHKR). Bone and muscle P content, plasma intact parathyroid hormone (iPTH) levels, P absorption, plasma P levels and urinary and fecal P excretion did not change in SVCR and UVCR compared with their pre-HK values. During HK, plasma P levels, urinary and fecal P excretion increased significantly (p<0.05) while muscle and bone P content, P absorption and plasma iPTH levels decreased significantly (p<0.05) in SHKR and UHKR compared with their pre-HK values and the values in their respective vivarium controls (SVCR and UVCR). During the initial 9-days of post-HK, plasma, urinary and fecal P levels decreased significantly (p<0.05), and plasma iPTH levels, muscle and bone P levels remained significantly (p<0.05) depressed in hypokinetic rats compared with their pre-HK values and the values in their respective vivarium control rats. By the 15th day, these values approached the control values. During HK and post-HK, changes in P absorption, plasma iPTH levels, and P levels in muscle, bone, plasma, urine and feces were significantly (p<0.05) greater in SHKR than in UHKR. Decreased tissue P content with increased P loss in animals receiving and not receiving P supplementation demonstrates decreased P deposition during HK. Higher P excretion with lower tissue content in SHKR and UHKR demonstrates that P deposition is decreased more with P supplementation than without. Because SHKR with a lower tissue P content showed higher P excretion than UHKR it was concluded that the risk of decreased P deposition with greater tissue P depletion is inversely related to P intake, that is, the higher the P intake the greater the risk for decreased P deposition and the greater tissue P depletion. It was shown that P (regardless of the intensity of its tissue depletion) is lost during HK unless factors contributing to the decreased P deposition are partially or totally reversed. It was concluded that dissociation between (decreased) tissue P content and (increased) P uptake indicates decreased P (absorption and) deposition as the main mechanisms of tissue P depletion during prolonged HK.     

Effect of artificial gravitation on the skeletal musculature of rats during space flights]

Comparative morphological and histochemical investigation of the rat skeletal muscles after a 18.5 days flight in the space ship "Cosmos-936" under conditions of weightlessness and artificial gravitation created by means of a centrifuge has demonstrated that weightlessness creates muscular atrophy, with fibres of different types affected in different muscles. The greatest changes take place in the soleus muscle. Metabolic disorders in the muscular tissue are manifested as an excessive deposition of glycogen and an increased content of phospholipids in it. The artificial gravitation favourably affects the state of the skeletal musculature preventing the development of metabolic disorders, though it does not completely avert the appearance of atrophic processes in it.