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The influence of insulin preparations (Actrapid and Ransulin) on the glucose and insulin blood level has been studied in patients with diabetes mellitus. It has been shown that comparable changes in the measured parameters are achieved in most patients with oral doses of Ransulin that are two to three times higher than the doses of Actrapid.

Oral administration of diluted solutions of insulin results in the absorption of the hormone into bloodstream. After oral administration of diluted insulin solutions to healthy volunteers and animals with experimental diabetes insulin does not undergo hydrolytic degradation under the action of proteolytic enzymes and its absorption is sufficient to produce the hypoglycemic effect. This approach gives a chance of creating of novel strategy for diabetes treatment.

Experiments on animals showed that native proteins may diffuse into the blood flow after oral administration of diluted protein solutions. An in vitro study led us to hypothesize that treatment with diluted solutions is accompanied by a decrease in the rate of protein proteolysis and accelerated protein diffusion through the intestinal mucosa.

In 73 elderly patients with type II sugar diabetes there were found changes of gustatory perception of sweet that were most pronounced on primary stage of the disease and that can be considered as manifestation of diabetic neuropathy of oral cavity organs and tissues.

Comprehensive stomatologic examination of 45 patients with chronic generalized parodontitis (CGP) was combined with parallel determination of immunoreactive insulin (IRI) in blood. In 30 patients CGP developed on the background of metabolic syndrome (MS). Clinical and X-ray examination of periodontal tissues disclosed that CGP in patients with MS was characterized by active and aggressive course. A correlation between CGP severity degree and level of IRI in blood was established.

Hirudotherapy was used in the treatment of 39 patients (10 male and 29 female) aged 28-58 years with chronic sialadenitis and sialadenosis. Control group consisted of 15 normal subjects without diseases of salivary glands. Lipid peroxidation (LPO) and antioxidant defense (AOD) parameters were under study. Hirudotherapy led to improvement of the clinical status in the majority of patients with sialadenosis; the content of superoxide dismutase (SOD) normalized and ceruloplasmin (CP) level increased. The status of patients with sialadenitis also improved; catalase and glutathione peroxidase levels normalized and SOD and CP levels increased. The best therapeutic effect was attained in patients with sialadenitis. No appreciable improvement was observed in patients with chronic parenchymatous parotitis in the presence of Sjogren's syndrome.

Aim: The study of insulin blood spectrum, capillary morphology (by evidence of skin biopsies), antithrombogenic activity of the vascular wall in patients with non-insulin-dependent diabetes mellitus; assessment of possible corrective therapy., Materials and Methods: 65 patients with type II diabetes mellitus (DM) entered the trial. Concentrations of free, bound, immunoreactive insulin (IRI) and C peptide were measured before and 10, 30, 60, 120 min after intravenous injection of glucose. Microcirculatory bed condition was evaluated by the data from skin biopsies. Antithrombogenic characteristics of the vascular wall were investigated at-test., Results: The tests discovered that DM patients had high IRI and low free insulin in high glucose levels; disorders of hemostasis, active proliferation in the microvessels. In patients with microangiopathy tiklid therapy given for 45 days reduced the speed and degree of platelet aggregation, improved fibrinolysis and clinical course of the disease., Conclusion: High level of IRI may be due to emergence of insulin-like substances dissociation of which produces peptides enhancing proliferative processes.

Altogether 24 adolescents with pubertal juvenile dyspituitarism (PJD) were investigated in the course of an oral GTT for 3 hours. The patients were divided into 3 groups: (1) with liver dysfunction and normal BP; (2) with normal liver and arterial hypertension; (3) with normal BP and normal liver function. The levels of glycemia, immunoreactive insulin, C-peptide and a molar C-peptide/insulin ratio were measured. All the examinees were characterized by basal and stimulated hyperinsulinemia against a background of a normal C-peptide value, the absence of a tendency to IRI reduction by the end of the GTT. A decrease in the C-peptide/IRI ratio was marked in the 1st group. One of the reasons of hyperinsulinemia in PJD in parallel with high insulin secretory pancreatic function can be a decrease in the metabolic clearance of liver insulin, especially noticeable in patients with hepatocyte dysfunction.

The paper is devoted to a study of the time course of lipid metabolism, analysis of glucose tolerance, change in indices of immunoreactive insulin, glucagon and C-peptide before the start of verapamil therapy and 6 mos. after it during monotherapy with this drug. These parameters were investigated in the blood serum using biochemical methods and radioimmunoassays. A marked antihypertensive effect was achieved in patients suffering from noninsulin dependent diabetes mellitus with concomitant essential hypertension of the 2nd degree. No negative effect on the pancreatic hormone secretion was noted. Lipid transport indices were improved.

Dilution of thrombocyte-rich blood plasma (down to 2.5 x 10(8) thrombocytes/ml) enabled to avoid an irreversible phase of the ADP-induced thrombocyte aggregation; the reversible phase of aggregation was followed by deaggregation. The reversible aggregation of thrombocytes was studied in healthy persons and patients with diabetes mellitus within wide ranges of ADP concentrations (including 10 microM) using the diluted blood plasma. Thrombocytes of the patients with diabetes mellitus of the I and II types were found to be 1.6- and 2.33-fold more sensitive to the ADP aggregating effect as compared with thrombocytes of healthy persons. The elevated rate of thrombocytes aggregation in diabetes mellitus appears to be related to early decrease in activity of thrombocyte guanylate cyclase and to its ability to be activated.

A comparative study of the effect of acute and chronic administration of sulfanilureal sugar lowering drugs (glipizide and glibenclamide) on the secretion of the pancreatic hormones, indices of microcirculation, the level of triglycerides and nonesterified fatty acids was conducted. Patients with primary detected diabetes mellitus with normal body mass and obesity of I-III degrees were investigated. The principal differences in insulinotropic action of sugar lowering drugs in various groups of patients and significant differences in the mechanism of their hypoglycemic action at varying time of treatment indicate the necessity of a strictly differentiated approach to subscription of these drugs for patients with primary detected diabetes mellitus.

In studying the formation of insulin complexes with transferrin the role played by sialic acids in this process was ascertained. The role of terminal sialic acids, included into the glycoprotein composition, in the formation of complexes of these glycoproteins with a number of components circulating in the blood was noted earlier. To study the role played by sialic acids of transferrin molecule in the formation of complexes with insulin the author used transferrin untreated and treated with neuraminidase, an enzyme splitting the sialic acid molecules from grycoprotein specifically. The influence of these preparations on the biological activity of insulin was studied. Transferrin devoid of sialic acid lost its capacity to form complexes with insulin. Control experiments demonstrated that by itself neuraminidase treatment of preparations of transferrin and insulin failed to influence their biological activity. The results of experiments with the use of neuraminidase demonstrated that sialic acid in donor transferrin molecule could be of great significance in the formation of an insulin-transferrin complex.

The effect was studied of synthetic tetradecapeptide-the fat-mobilizing human somatotropin fragment 31-34--on the fat content in fat depot and glucode concentration in the rabbit blood plasma and urine. A marked decrease in subcutaneous (the nape region), perirenal, mesenteric and epididimal fat content, accompanied by partial replacement of the fatty tissue by the connective one, was seen 3 to 4 weeks after tetradecapeptide injection to rabbits. Peptide effect manifested itself only under condition of the inadequate diet and was especially pronounced in young animals. Clucosuria and hyperglycemia were not observed after chronic tetradecapeptide injection. Tetradecapeptide did not exert an evident hyperglycemic or insulinogenous effect and did not produce a marked glucose tolerance fall after short administration to rabbits and during the glucose tolerance test in rats.

It was established that alimentary obesity in rats was accompanied by a considerable elevation of the blood insulin level. Under these conditions the number of receptors to insulin on the rat liver cell plasmatic membranes decreased 1 1/2 to 2 times depending on the obesity degree. The receptor affinity to the hormone remained unchanged. It was shown that the receptor density to insulin on adipocytes isolated from the rat fatty tissue was sharply reduced, the decrease being correlated with the biological effect lowering of insulin in this tissue.

Clear differences in properties of platelet guanylate cyclase from healthy donors and patients with diabetes mellitus were identified; departure from the norm was more pronounced in the case of the II-type of this disease, than the I-type. We have registered the decrease in the Mg-activity (basal) of guanylate cyclase by 30 and 50 per cent, Mn-activity--by 20 and 30 per cent, the state of guanylate cyclase activation by 0.1 mM sodium nitroprusside to 2 and 3-fold in patients with I and II-type of diabetes mellitus, consequently. The possible causative factors of these disturbances are discussed. It is suggested that the decrease in guanylate cyclase activation by nitroprusside is due to the enzyme heme-deficiency rising with the diabetes mellitus.

A study was made of the enzymes of the islands of Langerhans which could participate in the transformation of proinsulin into insulin. The homogenate of the islands of Langerhans of rat and man catalized the hyppuril-L-arginine splitting at pH 5.4-5.8 and 6.8-7.2 which was completely blocked with N-ethyl maleimide. The enzyme of the islands with the optimum action pH of 5.4-5.8 was similar to the enzyme of the exocrine tissue and was possibly a catheptic carboxypeptidase. The second enzyme of the islands differing from the exocrine carboxypeptidase could apparently participate in the insulin formation from the intermediate forms of proinsulin. In the formation of these proinsulin fomrs the participation of the enzyme of the endopeptidase character with a more acid optimum of the action pH is supposed.

The authors used oxyproline indices for the diagnosis of diabetic nephroangiopathies. Patients with diabetes mellitus of various severity (47 in all) were examined. Disturbance of oxyproline metabolism observed in these patients was particularly pronounced in development of nephroangiopathies; this can apparently be attributed to destruction of the basal membrane. The authors believe that it is difficult to assess the collagen metabolism in patients with diabetes mellitus by the urinary oxyproline content, since these patients display a disturbance of the glomerular function of the liver at various stages of the disease.

The paper is concerned with the results of investigation of 26 donors and 85 patients with diabetes mellitus, type II, with normal body mass and obesity during GTT and a test breakfast to reveal correlation of IRI and IRG levels with the level of gastrin. Comparative analysis of indices during OGTT and food intake has shown that an increase in the levels of gastrin in patients with diabetes mellitus, type II, does not correlate with body mass and the total level of insulin, but it may correlate with a metabolically active form of insulin. During food intake the levels of gastrin rise and do not change during GTT. A rise of the level of gastrin in patients with diabetes mellitus, type II, during a test breakfast is accompanied by change in the level of insulin, its peak being lower than that during GTT. Attention was focused on a group of patients with a history of obesity in whom by the time of investigation body mass returned to normal and the level of glucose was decreased. However, gastrin and insulin levels were still high, and metabolic regulation was disturbed. Therefore, body mass normalization did not eliminate causative and pathogenetic factors of diabetes mellitus.

Insulin secretion was studied in comparison with the glucose level in persons with disturbed glucose tolerance and in patients with type II diabetes mellitus using a glucose tolerance test and with regard for an obesity degree (the body weight index). The hyperinsulinism incidence in these groups was determined versus that of the controls. The correlation between a high insulin response and the glucose level was absent. Insulin-red blood cell binding was studied in patients with hyperinsulinism and disorder of this process was demonstrated. The hyperinsulinism rate decreased after the body weight index and the glucose level returned to normal.

A study was made of levels of malonic dialdehyde, peroxide hemolysis of erythrocytes, superoxide dismutase activity and a tocopherol content for the purpose of investigating the state of lipid peroxidation in 14 patients with type I diabetes mellitus. Correlation between the state of lipid peroxidation and a degree of diabetes mellitus compensation was established. Decompensated diabetes mellitus was characterized by more enhanced lipid peroxidation and tocopherol deficiency.

A study was made of the capacity of insulinoma to catalyze the splitting of hippuryl-L-arginine (HA) and the contents of proinsulin-like component in the tissues of the tumours and in the blood serum of the patients. As revealed, in the absence of HA splitting by the tumour cytoplasmic fraction in the neutral pH zone there was noted a higher proinsulin-like component both in the tumour tissue and in the blood serum. An increase amount of proinsulin-like component in the blood serum stipulates possibly a more prolonged period of starvation before the occurrence of hypoglycemia, and a less pronounced picture of hypoglycemia in such patients in comparison with the patients whose tumours were capable of splitting HA similarly to the normal islands of Langerhans.

The level of pancreatic hormones was studied in 10 healthy persons and in 40 patients with diabetes mellitus detected for the first time by GTT, their body mass being normal. For assessment of immunoreactive insulin (IRI), the level of proinsulin and biological activity of serum insulin were determined, and these indices were compared with glucose and C-peptide levels. The examinees' inhomogeneity was shown; on the basis of the findings obtained 2 groups were identified. A decrease in the levels of IRI, C-peptide and biological activity of serum insulin in the 1st group indicated a possibility of type I diabetes mellitus in such patients. Hyperinsulinemia, not correlating with glucose and C-peptide, a high percentage of proinsulin and low biological activity of serum insulin were noted in the 2nd group. The study permitted a differentiated approach to assessment of patients and a choice of therapeutic tactics.

Indices of acid-base equilibrium (ABE), the level of ketone bodies, coagulation and platelet procoagulant hemostasis, and erythrocyte aggregation were studied in 102 patients with diabetes mellitus, of them in 58 patients with diabetic ketoacidosis and in 10 practically healthy persons. The most frequent cause of the development of diabetic ketoacidosis was poorly controlled treatment of diabetes and infections. The most frequent type of ABE disorder in patients with diabetic ketoacidosis was metabolic acidosis with secondary compensatory respiratory alkalosis. Ketoacidosis was characterized by hemostatic disorders after hypercoagulation type, an increase in platelet and erythrocyte aggregation activity with secondary activated fibrinolysis.

Study on the insulin--receptor interaction of the plasma membranes of liver cells demonstrated a reverse dependence of insulin concentration in the blood and the number of insulin-binding sites on the membranes. Using isolated adipocytes, it was shown that at a constant number of receptors the receptor density is changed. These changes are correlated with the decrease of biological effects in experimental obesity accompanied by hyperinsulinism. In the case of streptosotocin diabetes (simulated hypoinsulinism) no correlation between insulin binding and its biological effects was observed, which can be accounted for by disturbances in transmission of the signal from the insulin--receptor complex to the enzymatic systems of the cells.

Insulin and glucagon levels and their molar ratio were examined in patients with medium severity diabetes mellitus and stage I-III obesity given sugar-reducing drugs perorally. Immunoreactive insulin and immunoreactive glucagon, levels varied within broad limits, with a trend to increase in the majority of patients. Both low (1.4) and high (10.9) molar ratios of insulin and glucagon were observed (it comprised 3.4 in the control group). The degree of obesity did not always correlate with the molar ratio or with the immunoreactive insulin level. During treatment a trend for normalization of the insulin/glucagon molar ration was noted. The insulin/glucagon ratio may be used as an index of the efficacy of the treatment.

Clinical studies of domestic purified insulin agents were performed in 35 patients (26 males and 9 females, aged 20 to 40 years old) suffering from I type diabetes mellitus. Among these patients 4 were with a labile disease course and 2 with insulin resistance. The effectiveness of the drugs mentioned was evaluated according to the acquired diabetes mellitus compensation, concerning carbohydrate metabolism, the diurnal variations in insulin requirement and anti-insulin antibody titer and a changed diabetes mellitus course. The purified insulin agents were effective in I type diabetes mellitus patients. They did not differ from the ordinary domestic drugs (su-insulin) by their hypoglycemic activity. The terms of diabetes compensation became shorter, the lability was removed and insulin resistance was overcome in some patients, using these drugs. The decreased antiinsulin titer and diurnal insulin requirement were noted in the majority of the patients.

A modified method for isolation of Langerhans islands from rat pancreas is described. The islands obtained were free from acinous tissue as shown by means of an amylase test and by microscopy. In homogenates of the islands proteolytic activities were observed (pH optimum at 5.3--5.5 and 6.9--7.2).

The structural correlates of the cell responses in subnuclei of the hypothalamic paraventricular nuclei (PVN) in fasting and carbohydrate loaded adult male rats were studied using light microscopic morphometric methods. The data obtained revealed difference in responsiveness of the subnuclei studied to alternative shifts in the carbohydrate homeostasis: histophysiological features in five of ten cell-divisions, distinguished in the rat RVN, demonstrated their dependence on impaired carbohydrate homeostasis.

Patients with types I and II diabetes mellitus without the clinical signs of nephroangiopathy were subjected to a comprehensive study of renal function. Using the method for determination of endogenous creatinine clearance (140 patients), radionuclide methods (in 350 patients) and beta-2-microtest (in 130 patients) the impairment of renal filtration function was established in 30.8, 67.6 and in 52% of the patients, respectively. In 16.3% of the patients, there was an impairment of the proximal part of the canaliculi. The determination of proteinuria selectivity in polyacrylamide gel revealed latent proteinuria in 70% of the patients and enabled one to specify the spectrum of uroproteins. The informative value of the methods suggested was supported by the results of morphologic studies of biopsy specimens of the kidneys and skin. The importance of the specification of the preclinical stage of diabetic nephroangiopathy was determined by the possibility of the reverse development of the pathological alterations at the given stage. The authors describe the experience gained with the correction of functional disorders by means of programmed administration of insulin using the apparatus Biostator, application of diamicron and angioprotectors.

The spectra and activities of isozymes of hexokinase and alcohol dehydrogenase (enzymes that catalyse glucose and ethanol assimilation), glucose-6-phosphate dehydrogenase (the key enzyme of the pentose phosphate shunt) and malate dehydrogenase (an enzyme of the tricarboxylic acid cycle) were comparatively studied in Pichia pinus haploid (MH4) and autodiploid (D4) strains. Differences in the qualitative composition of the isoenzyme spectra and activities suggest that the intensity and the role of the studied metabolic pathways and cycles differ between the haploid and autodiploid strains of Pichia pinus.

The authors present for the first time their results concerned with the determination of selective proteinurea by disc electrophoresis in polyacrylamide gel in patients with insulin-dependent and insulin-independent diabetes mellitus with and without the clinical signs of kidney affection. A study was made of the uroproteinograms of these patients before and after the correction of carbohydrate metabolism by means of programmed insulin administration. A conclusion was made of a possibility to use the above method for early detection of diabetic nephropathies. Programmed insulin administration using the Biostator apparatus was shown to improve tubuloglomerular functions, that was expressed in the lowering of proteinurea and in some cases in the improving of the qualitative composition of uroproteins.

The character of the insulin effect on the activity of phosphodiesterase (PDE) cAMP of various subcellular localization was studied in the liver of normal and diabetic rats. As a result of kinetic investigations for PDE cAMP preparations of the plasma membranes there were obtained kinetic characteristics of two PDE forms, differing by their affinity to the substrate. For the both PDE cAMP forms stimulation of the activity with insulin was indicated. In examining the insulin effect on the activity of PDE cAMP of the liver of rats with streptozotocin-induced diabetes there was revealed a significant effect of the hormone on the kinetics of the enzyme with a high affinity to cAMP only.