Subetta Enhances Sensitivity of Human Muscle Cells to Insulin.

Addition of Subetta to insulin (10 nM) increased insulin-stimulated glucose uptake 43% (p<0.001). Moreover, glucose uptake stimulated by insulin (10 nM) in the presence of Subetta was similar to that stimulated by 300 nM insulin. These findings suggest that Subetta significantly enhanced insulin sensitivity of tissues through stimulation of glucose transport to myocytes mediated by glucose transporter 4.

Subetta increases phosphorylation of insulin receptor ß-subunit alone and in the presence of insulin.

It has been previously shown that Subetta (a drug containing released-active forms of antibodies to the insulin receptor ß-subunit and antibodies to endothelial nitric oxide synthase) stimulated insulin-induced adiponectin production by mature human adipocytes in the absence of insulin. Therefore, it was assumed that Subetta could activate the insulin receptor. To confirm this hypothesis, the capacity of Subetta to activate the insulin receptor in mature human adipocytes in the absence or presence of the insulin was investigated. Cells were incubated either with Subetta or with vehicle, or with basal medium for 3 days. Then, adipocytes were treated with water or insulin (100 nm) for 15 min. Following treatment, lysates were prepared and phosphorylation of insulin receptor ß-subunits was analyzed by western blot analysis. It was shown that Subetta significantly increased (P<0.001) the 'phosphorylated-insulin receptor ß-subunit/total insulin receptor ß-subunit' ratios in both the presence and the absence of insulin. These results support previously published data and indicate that Subetta could activate the insulin receptor through the effect on its ß-subunits, whose conformational state is essential for insulin receptor activation. This action might serve as one of the primary mechanisms of the drug's antidiabetic effect.

[Perspectives of the novel drug divaza in the treatment of chronic cerebral ischemia].

The present paper reviews preclinical research of divaza, the combination of release-active antibodies to brain-specific 5100 protein and release-active antibodies to endothelial NO-synthase. Preclinical studies have revealed that the specific pharmacological activity of the compounds is retained in the combination, and the components mutually potentiate each other's effects. The previous research have demonstrated high efficacy of divaza in the experimental models of cerebral ischemia and neurodegenerative diseases. Divaza also displays the antihypoxant and antioxidant activity in the animal models of hypoxia by reducing the pathological changes of brain tissue. Significant reduction of the lipid peroxidation process in the affected brain regions can be one of the mechanisms of this effect. In standard experimental models of anxiety and depression, divaza positively influences the psycho-emotional state of animals.

[Activity of the skeletal muscle proteolytic systems during functional unloading].

The recovery of the skeletal muscle structure and function after prolonged disuse is the problem of the rehabilitation and space medicine great concern. Hypokinesia affects mainly the postural muscles responsible for the support reaction. Atrophy developed under disuse is the result of the protein synthesis and proteolysis balance shift. Several signaling systems regulating proteolysis are known now, though only recently researchers paid attention to the question whether these systems work identically in the muscles atrophied under different stimuli (denervation, starvation etc.). In this review we aimed to summarize and analyze cumulative data concerning the work of the different proteolytic systems during the atrophy caused by hypokinesia and/or hypogravity. Also we discuss here the latest data about the interconnection of the signaling systems regulating the structural and functional muscle proteins degradation and synthesis under disuse.

Various jobs of proteolytic enzymes in skeletal muscle during unloading: facts and speculations.

Skeletal muscles, namely, postural muscles, as soleus, suffer from atrophy under disuse. Muscle atrophy development caused by unloading differs from that induced by denervation or other stimuli. Disuse atrophy is supposed to be the result of shift of protein synthesis/proteolysis balance towards protein degradation increase. Maintaining of the balance involves many systems of synthesis and proteolysis, whose activation leads to muscle adaptation to disuse rather than muscle degeneration. Here, we review recent data on activity of signaling systems involved in muscle atrophy development under unloading and muscle adaptation to the lack of support.

[Insulin-like growth factor 1 and the key markers of proteolysis during the acute period of readaptation of the muscle atrophied as a result of unloading].

It has been shown that, after prolonged disuse, the accumulation of muscle mass and the recovery of soleus fibers volume are caused by water accumulation rather than protein synthesis intensification. At the same time, expression rate of the main markers of the activity of ubiquitin-proteasome system remained increased on the 3rd day of reloading and decreased to the control by the 7th day. Both the quantity of the insulin-like growth factor 1 and the number of satellite cells fused with muscle fibers and of myonuclei began to increase only on the 7th day of reloading. The data obtained evidenced a significant inertness of the postural muscle during its adaptation to the load (normal gravity) after prolonged disuse.

[Contractile properties of the isolated rat musculus soleus and single skinned soleus fibers at the early stage of gravitational unloading: facts and hypotheses].

The contractile properties of the postural rat soleus muscle at the early stage of the gravitational unloading (3-day rat hindlimb suspension) have been studied using different modes of muscle contraction (twitch and tetanic contraction of the isolated muscle, Ca-induced contraction of isolated skinned fibers). A significant enhancement of the twitch maximal tension of unloaded muscles without changes in time-dependent characteristics was observed, although the half-relaxation time tended to increase. The fiber diameter did not change (42.37 +/- 0.76 vs 43.43 +/- 1.15 microm in controls). The Ca-induced maximal isometric tension in unloaded soleus was significantly decreased (32.1 +/- 1.05 vs 37.6 +/- 1.52 mg in controls, p < 0.05). The maximal specific tension was respectively decreased (23.14 +/- 0.77 vs 27.6 +/- 2.36 kN/m in controls). The pCa50 in unloaded muscle decreased from 6.05 +/- 0.02 in controls to 5.97 +/- 0.02 (p < 0.05), indicating the loss of myofibrillar calcium sensitivity. The analysis with the calcium probe Fluo-4AM demonstrated that the intracellular [Ca2+] was sufficiently increased after hindlimb suspension. At the same time, the relative content of titin and nebulin did not change.

[Mitochondrial ATP-dependent potassium channel. 1. The structure of the channel, the mechanisms of its functioning and regulation].

The modern conceptions of the structural organization and functional mechanisms of mitoKATP are discussed in the present review. Methods of the identification of the channel in the inner mitochondrial membrane and in intact cells are considered. The structure and properties of the channel, the mechanisms of its regulation with pharmacological modulators, redox agents (SH agents, NO and ROS), hormones etc. are reviewed. The authors adduce their own data concerning the structural organization, regulation, properties and the functional role of mitoKATP in the cell.