[Synthesis and hypoglycemic activity of bis(L-malato)oxovanadium(IV)].

In order to create new oral vanadyl organic complexes-based drugs for the treatment of diabetes mellitus biligand vanadyl derivative of L-malic acid (bis(L-malato)oxovanadium(IV) was prepared and its potential as a novel hypoglycemic agent was studied in the streptozotocin-diabetic rats. We show that the oral administration of bis(L-malato)oxovanadium(IV) with drink water significantly reduced glucose concentration in blood and urine, as well as the level of glycated proteins in the streptozotocin-diabetic rats.

[Modern approaches to pharmacotherapy of diabetes mellitus type II]. / Sovremennye podkhody k farmakoterapii sakharnogo diabeta II tipa.

The pharmacological approaches to the treatment of type 2 diabetes mellitus were reviewed. Special attention was paid to the new therapeutic agents that are able to decrease plasma glucose levels. The possible mechanisms of the hypoglycemic effects are discussed. Briefly, repaginide, nateglinede and alpha-glucosidase inhibitors prevent postprandial hypoclycemia while thiazaolidinediones improve the sensitivity to insulin and vanadium compounds act as an insulin action enhancer.

[Vanadium compounds--a new class of therapeutic agents for the treatment of diabetes mellitus]. / Vanadiisoderzhashchie soedineniia--novyi klass terapevticheskikh sredstv dlia lecheniia sakharnogo diabeta.

Vanadium compounds as insulin mimics with promising therapeutic properties are reviewed. The biological effects of both inorganic forms of vanadium and vanadyl organic complexes are decried for various animal models. These effects include hypoglycemic and insulin reserve actions, insulin sensitivity enhance, cholesterol lowering and other manifestations. The effectiveness of vanadium compounds in diabetes treatment is confirmed with clinical trials. The possible mechanisms of insulin-like effects of vanadium are discussed. The various nutritional supplements for patients with diabetes mellitus including vanadium-contained used in Russia and abroad are also considered.

[Comparative characteristics of vanadium-containing compounds, possessing insulin-like effects]. / Sravnitel'naia kharakteristika vanadii-soderzhashchikh soedinenii, obladaiushchikh insulino-podobnym deistviem.

The serum glucose concentration, HbAc1, fructoseamine, the activity of AST, ALT, amylase, glycogen content and glucokinase activity in rat hepatocytes were examined in streptozotocin-diabetic rats during long-term orthovanadate and vanadyl sulphate treatment. The improvement of this parameters were demonstrated after oral orthovanadate and vanadyl sulphate administration. However, insulin-mimetic properties of vanadyl sulphate were more marked in comparison with orthovanadate. LD-50 and cytotoxicity analysis in isolated hepatocytes showed that vanadyl sulphate was less toxic than orthovanadate.

[Changes in the level of fructose-2,6-biphosphate in peripheral blood lymphocytes in patients with diabetes mellitus]. / Izmenenie soderzhaniia fruktozo-2,6-bifosfata v limfotsitakh perifericheskoi krovi bol'nykh sakharnym diabetom.

Variation of fructose 2,6-bisphosphate (F-2,6-P2) content in the peripheral blood lymphocytes of patients with diabetes mellitus (type II) was investigated. The 2.5-fold increase of F-2,6-P2 level compared with to the control group was observed in untreated patients with early stage of the disease. In patients using of peroral antidiabetic drugs that corrected diabetes F-2,6-P2 level was approached to the normal one. At the same time F-2,6-P2 content decreases in patients with severe (noncorrected) diabetes mellitus. The possible mechanisms of regulation of lymphocyte F-2,6-P2 concentration in normal conditions and diabetes mellitus are discussed.

[Effect of oral inulin administration on the fructose 2,6-biphosphate level in the liver tissue of rats with streptozocin diabetes]. / Vliianie peroral'nogo vvedeniia inulina na uroven' fructozo-2,6-bifosfata v tkani pecheni krys pri streptozototsinovom diabete.

The influence of oral inulin administration on glucose and fructose content in blood, glucose and ketone bodies in urine, and fructose-2,6-diphosphate content in liver was investigated in rats with streptozotocin diabetes. Short-term administration (during 5-6 days) of 0.5% inulin solution caused three-fold increase of blood fructose compared with control, normalisation of blood glucose and disappearance of glucose- and ketoneuria. The level of fructose-2,6-di-phosphate in liver increased to the control level. Inulin administration during 12 days caused five-fold increase of blood fructose compares with control, glucose level increased up to the level of uncurred diabetes (22 mmol/1), glucose- and ketoneuria appeared. The content of fructose-2,6-diphosphate in the liver decreased to diabetic level.

[Functional characteristics of fructose-2,6-bisphosphate system in the liver during experimental streptozotocin diabetes]. / Nekotorye osobennosti funktsionirovaniia sistemy fruktozo-2,6-bisfosfata v tkani pecheni pri éksperimental'nom streptozototsinovom diabete.

The activity of phosphofructokinase-2, fructose, 1,6-bisphosphatase, glucokinase, and also the level of fructose 2,6-bisphosphate and glycogen were examined in the liver of normal, and streptozotocin-diabetic rats. It was shown that the activity of phosphofructokinase-2 was decreased in the liver of diabetic rats. Besides that the activity determined at pH 6.6 (the "active" or unphosphorylated enzyme form) was 3-fold reduced whereas the "total" enzyme activity as measured at pH 8.5 was lowered 1,7-fold. The phosphofructokinase-2 activity assay at two pH values allows to estimate a degree of phosphorylation of bifunctional enzyme which is markedly enhanced in diabetes. The fall of the bifunctional enzyme k in case activity is accompanied by the lowered fructose 2.6-bisphosphate level, increased fructose 1,6-bisphosphatase activity that in turn favours the liver tissue glycolysis inhibition and gluconeogenesis enhanced in diabetes.

[Fructose-2,6-bisphosphate system and experimental states]. / Sistema fruktozo-2,6-bisfosfata i éksperimental'nye sostoianiia.

The molecular mechanisms of the inhibitory action of fructose- 2,6-bisphosphate (F-2,6-P2) on fructose-1,6-biphosphatase (FB-Pase-1), the key enzyme of gluconeogenesis, and the those of the activating action of F-2,6-P2 on phosphofructo-1-kinase (PFK-1), the key enzyme of glycolysis, NMR spectroscopy first provided direct evidence for the fact that F-2,6-P2 was involved in the regulation of the sedoheptulose cycle of a nonoxidative stage of the pentosephosphate pathway. Procedures were developed in measuring the levels of F-2,6-P2 in the cell of experimental animal tissues and human blood lymphocytes. Naturally different emergencies substantially affected the F-2,6-P2 system by triggering these or those mechanisms controlling the activity of enzymes of this system. Vanadium-containing compounds were demonstrated to have a positive action on carbohydrate metabolism in diabetic (streptozotocin-induced) rat hepatocytes.

[Effect of soybean protein isolate on energy substrate oxidation in patients with insulin-dependent diabetes mellitus]. / Vliianie izoliata soevogo belka na okislenie énergosubstratov u bol'nykh insulinzavisimym sakharnym diabetom.

Using indirect colorimetry, the authors demonstrated disordered energy metabolism at rest in patients with insulin-dependent diabetes mellitus (IDDM) with a moderate decompensation of metabolism: carbohydrate oxidation was reduced and fat and protein oxidation increased, this being aimed at maintenance of the basic metabolism within the normal range under conditions of insulin insufficiency. Improvement of common parameters of compensation during optimization of insulin therapy and therapeutic diets was associated with approximation of substrate oxidation structure and energetic structure of a diet, as well as with increased production of useful energy coupled with reduced oxygen consumption. Moreover, a positive correlation between insulin level and carbohydrate oxidation rate was revealed. Analysis of the effects of qualitative composition of protein showed a more rapid improvement of metabolism during metabolic diet, whereas during therapy with diets including soybean protein increase of metabolism efficacy is more manifest. Bioenergetic parameters may be used as criteria of the efficacy of IDDM treatment. Changes in these parameters not always correlate with the time course of routine criteria of compensation and provide supplementary information on a patient's metabolic status.

[Preparation and use of an affinity sorbent containing phenylboric acid, for separation and quantitative determination of glycated hemoglobin]. / Poluchenie i ispol'zovanie afinnogo sorbenta, soderzhashchego fenilbornuiu kislotu, dlia razdeleniia i kolichestvennogo opredeleniia glikirovannogo gemoglobina.

m-Aminophenylboric acid, attached to epoxy-activated diasorb, developed a highly effective sorbent intended to separation and quantitative estimation of glycated hemoglobin. The procedure developed is reproducible, fast and may be used in mass scale examination of people for occult diabetes. Temperature and pH of buffers used did not affect significantly the data obtained.

[Behavior of ketoamine in animals]. / Povedenie ketoamina v organizme zhivotnogo.

A simple ketoamine 14C-fructosoglycine with all the fructose carbon atoms labelled was synthesized for studies of possible pathways of the ketoamines metabolism in animal body. The ketoamine bond in the fructosoglycine was not hydrolyzed during incubation with homogenates of rabbit liver, kidney, spleen and testicular tissues within 3 hrs at pH 4.8 and 7.3 as well as after hydrolysis with pancreatine (the enzymatic extract from bovine pancreas) at pH 8.4. 14C-fructosoglycine administered into rabbit circulation was mainly excreted with urine (about 70% of the label) within 8-14 days. The main part of the ketoamine was excreted as fructosoglycine and the lower amount--as glycated dipeptide; some amount of fructosoglycine was hydrolyzed liberating fructose or converted into aldimine which was hydrolyzed with formation of glucose. The ketoamine was metabolized also into non-reducing isosucrose-like glucofructoside, insensitive to acid and enzymatic hydrolysis.

[The effect of hyperbaric oxygenation on glycosylated proteins in diabetes mellitus]. / Vliianie giperbaricheskoi oksigenatsii na glikirovannye belki pri sakharnom diabete.

Hyperbaric oxygenation (HBO) effects on the levels of circulating glycosylated proteins with various life spans in the blood stream (glycosylated hemoglobin (GH) and serum glycosylated fructose amine (SF) were studied in diabetes mellitus patients not suffering from vascular complications but developing various microangiopathies. Measurements of blood glycosylated proteins and mean daily glycemia carried out over the course of HBO treatment in the diabetics without microangiopathies evidenced an essential reduction of blood GH, SF, and glucose, reaching, in some cases, the normal values. Patients with vascular involvement (lower limb angiopathy, nephropathy, retinopathy) exposed to HBO developed but a trend to reduction of blood levels of glycosylated proteins and glucose. These results indicate a positive therapeutic effect of HBO courses on the status of diabetics with slightly manifest microvascular involvement. In cases with grave vascular involvement exposure to HBO appears inefficient.

[A colorimetric method of determining non-enzymatically glycosylated albumin and hemoglobin]. / Kolorimetricheskii metod opredeleniia nefermentativno glikozilirovannogo al'bumina i gemoglobina.

A method for measuring non-enzymatically glycosylated albumin and hemoglobin in a single blood sample is described. It is advisable that these proteins be assayed separately, because albumin metabolism rate is higher than that of hemoglobin and therefore glycosylated hemoglobin may be regarded as a criterion for diagnosing diabetes mellitus and the level of glycosylated albumin as an indicator of diabetes mellitus compensation and a characteristic that permits monitoring the course of treatment. The method consists in preparation of the blood erythrocytic mass and plasma, followed by trichloracetic acid hydrolysis of glycosylated hemoglobin and glycosylated albumin during heating and assay of the resultant fructose forming a colored complex with thiobarbituric acid. Twenty-nine normal subjects were examined with the use of this method; the mean arithmetic (means +/- m) has made up 3.68 +/- 0.21 mumols of fructose glycine per g of hemoglobin for glycosylated hemoglobin and 27.0 +/- 1.78 mumols of fructose glycine per g of albumin for glycosylated albumin. In diabetics these values were several times higher and the mean arithmetic value of glycosylated hemoglobin was 20.5 +/- 0.45 mumols of fructose glycine per g of hemoglobin and that of glycosylated albumin 63.8 +/- 1.7 mumols of fructose glycine per g of albumin (n = 42), the significance of differences being p less than 0.001.

[The effect of sorbitol on the determination of keto amines using a colorimetric method]. / Vliianie sorbita na opredelenie ketoaminov kolorimetricheskim metodom.

The presence of sorbitol in a concentration 11 mg/ml in a sample reduces by 68 percent the values of fructose glycine measured by colorimetry with thiobarbituric acid. Such sorbitol concentration has no effect on furfural production and on 5-hydroxymethylfurfural reaction with thiobarbituric acid. Measurements of glycolyzed hemoglobin have demonstrated that sorbitol in concentration 11 mg/ml completely inhibits hydrolysis. This fact should be borne in mind when measuring blood glycosylated hemoglobin by colorimetry with thiobarbituric acid and exclude sorbitol from patients' rations before measurements.

[A colorimetric method for determining nonenzymatically glycosylated hemoglobin in human blood]. / Kolorimetricheskii metod opredeleniia nefermentativno glikozilirovannogo gemoglobina v krovi cheloveka.

A simple quantitative procedure is described for estimation of nonenzymatically glycosylated hemoglobin (HbAIc) in blood, which involved acid hydrolysis of hemoglobin in trichloracetic acid with heating. The liberated fructose was measured by development of colour complex of 5-hydroxymethyl furfurol (produced from fructose in acid solution) and thiobarbituric acid. Estimation of HbAIc was carried out in 30 healthy persons and in 50 patients with diabetes of the I type using the procedure developed. Concentration of HbAIc constituted 3.0 +/- 0.15% of total Hb in healthy persons, while its content was increased up to 7.0 +/- 0.5% in patients with diabetes of middle severity and up to 20% and higher in patients with severe forms of the disease. The procedure developed is recommended for use in laboratories of wide profile for diagnosis of diabetes.