Platelet hemostasis in patients with metabolic syndrome and type 2 diabetes mellitus: cGMP- and NO-dependent mechanisms in the insulin-mediated platelet aggregation.

Patients with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) have high risk of microcirculation complications and microangiopathies. An increase in thrombogenic risk is associated with platelet hyperaggregation, hypercoagulation, and hyperfibrinolysis. Factors leading to platelet activation in MetS and T2DM comprise insulin resistance, hyperglycemia, non-enzymatic glycosylation, oxidative stress, and inflammation.

[Phenazine methosulfate system-induced membrane hyperpolarization in the human erythrocytes].

Erythrocyte membrane potential was recorded via measurement of pH of the incubation medium in presence ofprothonophore. The increase of intracellular calcium concentration in presence of calcium ionophore A23187 and addition of the artificial redox-system ascorbate-phenazine methosulfate led to membrane hyperpolarization due to opening of Ca(2+)-activated potassium channels that are regulated by multiple signaling pathways. The opening of the Ca(2+)-activated potassium channels in presence of artificial redox-system ascorbate-phenazine methosulfate is mediated at least by two mechanisms including an increase in affinity of channels to calcium ions and involvement of the protein SH-groups and the components of the respiratory circuit which have beer found in erythrocyte membrane.

Effect of insulin on Ca(2+)-dependent hyperpolarization in erythrocytes from healthy donors and patients with type 2 diabetes mellitus accompanied by arterial hypertension.

Insulin decreased A23187-induced hyperpolarization of the erythrocyte membrane in healthy donors. These data indicate that insulin plays a role in the regulation of Ca(2+)-activated potassium channels in human erythrocytes. However, insulin had little effect on hyperpolarization response of cells induced by artificial ascorbate--phenazine methosulfate donor-acceptor system.

Effect of insulin on NO production by monocytes from patients with metabolic cardiovascular syndrome.

Basal and insulin-induced production of NO by monocytes significantly increased in patients with metabolic cardiovascular syndrome. Plasma insulin concentration in these patients was below the control. No intergroup differences were found in C-peptide concentration.

Volume-dependent regulation of Ca2+-activated potassium channels in erythrocytes from healthy donors and patients with type II diabetes mellitus aggravated by arterial hypertension.

Increase in intracellular Ca2+ concentration caused by calcium ionophore A23187 or ascorbate+phenazine methosulphate electron donor system added to erythrocyte suspension induced similar shifts in erythrocyte membrane potential. These processes are most likely mediated by Ca2+-activated potassium channels. Changes in the osmolarity of the incubation medium produced opposite effects on membrane hyperpolarization induced by A23187 or ascorbate+phenazine methosulphate in erythrocyte isolated from healthy donors, which attests to the existence of different mechanisms of regulation of Ca2+-activated potassium channels.

Effect of lipid matrix and cytoskeleton proteins on Ca2+-activated K+ channels in erythrocytes of alcoholic and II type diabetes mellitus patients.

We studied the effect of changes in erythrocyte volume and irreversible thermal denaturation of cytoskeleton proteins and lipid matrix on activity of Ca(2+)-activated K+ channels in erythrocytes of alcoholic and patients with II type diabetes mellitus. Changes in Ca(2+)-dependent potassium permeability of erythrocyte membrane in alcoholic patients and patients with II type diabetes mellitus are related to modification of cytoskeleton, rather than to changes in lipid matrix.

[Insulin secretion by isolated rat pancreas as affected by prooxidants; relationship to glutathione release].

Rates of basal and glucose-stimulated insulin and glutathione secretion were studied in experiments with isolated rat pancreas, as were prooxidant effects on these values. The rate of oxidized and recovered glutathione release was found increased at glucose concentration increase to 16.7 mmoles in perfusion solution.

[The effect of pro-oxidants on insulin secretion by the isolated rat pancreas].

The effect of pro-oxidants (tert-butyl peroxide and FeSO4) on rats perfusing isolated pancreas insulin secretion was studied. Pro-oxidants (10(-4) M) preperfusion during 20 minutes did not change significantly the basal insulin secretion and decreased glucose-stimulated secretion of the one. The content of pancreas TBA-active products increased twice after pro-oxidants effect and ratio of reduced and oxidized glutathiones liberation rates decreased from 2 to 0.

[Mechanism of involvement of calmodulin in the regulation of affinity to Ca2+ and maximum activity of Ca-pump in the erythrocyte membrane].

The activity of the Ca-pump in inside-out oriented human erythrocyte membrane vesicles was studied with the use of 45Ca and membrane filters. It was found that trifluoroperazine fully inhibits the calmodulin-induced increase in the maximal activity of the Ca-pump without affecting the calmodulin-stimulated increase in the Ca-pump affinity for Ca2+. The dependence of calcium concentrations of calmodulin-stimulated components of the Ca-pump activity, both inhibited and noninhibited by trifluoroperazine, as well as the dependence on calcium concentrations of the fluorescence intensity of N-phenyl-1-naphthylamine were analyzed.

[Mechanism of the effect of EGTA on the affinity to calcium of Ca-transporting and Ca-binding cell systems].

The activity of Ca-ATPases of erythrocyte ghosts and sarcoplasmic reticulum and the rate of ATP-dependent uptake of 45Ca by erythrocyte membrane inside-out oriented vesicles, sarcoplasmic reticulum vesicles and mitochondria were investigated. It was found that in all cases studied the addition of EGTA to the incubation mixture caused an increase in the affinity of Ca-pumps for Ca2+; their maximal activity remained thereby unaffected. A similar effect of EGTA was observed when the affinity for Ca2+ of calmodulin, troponin C and the fluorescent dye quin 2 were determined.

[The role of free calmodulin in the regulation of calcium-pump activity in erythrocytes].

The activity of Ca-pump in inside-out oriented vesicles obtained from erythrocyte membranes after their 30 min treatment with EGTA at 20 degrees C (membranes A) and 37 degrees C (membranes B) was investigated. It was shown that in membranes A placed into an incubation medium containing 0.1 mM EGTA (pH 7.