[Glucose tolerance disorders in patients with hypothyroidism]. / O narusheniiakh tolerantnosti k gliukoze u bol'nykh gipotireozom.

Altogether 42 patients with hypothyrosis of different etiology (aged 17 to 57) were investigated. According to the results of oral glucose tolerance test (OGTT) all the patients were divided into 3 groups: normal OGTT, disturbed OGTT and a flat type of glycemic curves. High levels of cortisol and free fatty acids (FFA) were detected in persons with disturbed OGTT. A lowered reaction to insulin was found in 15 patients with high levels of cortisol and FFA. Persons with unchanged sensitivity to insulin demonstrated a normal type of OGTT and normal blood levels of cortisol and FFA, and among patients with a low reaction to insulin there were persons with disturbed OGTT and high blood levels of cortisol and OGTT. Positive correlation was found between OGTT disturbances, on the one hand, and lowered sensitivity to insulin, increased blood levels of cortisol and FFA, on the other hand. A conclusion has been made that one of the causes of GTT disturbance in patients with hypothyrosis is an increase in the blood levels of cortisol and FFA and a decrease of sensitivity to insulin.

[Hypoglycemic activity of bicyclic diterpenoids of the clerodane series as compared to adebit and maninil]. / Izuchenie gipoglikemicheskoi aktivnosti bitsiklicheskikh diterpenoidov klerodanovogo riada v sravnenii s adebitom i maninilom.

Biocyclic diterpenoids--salvin, salvicin and salvifolin, administered per os to rats at a dose of 50 mg/kg show marked hypoglycemic activity in intact animals as well as in animals with experimental hyperglycemia developing against a background of GTT (3000 mg/kg intraperitoneally) or alloxan (150 mg/kg subcutaneously). They are superior to adebit but inferior to maninil. Prophylactic and therapeutic administration of these compounds ensure the preservation of islet beta-cells in animals with alloxan diabetes.

[Causes of development of the diabetic syndrome in patients with diffuse toxic goiter]. / Prichiny razvitiia diabeticheskogo sindroma u bol'nykh diffuznym toksicheskim zobom.

Altogether 41 patients with thyrotoxicosis of mean severity at the stage of decompensation were observed. By glucose tolerance they were divided into 3 groups: with normal, flat and disturbed curves. The third group vs. the first group demonstrated higher levels of the thyroid hormones, cortisol and insulin. C-peptide/insulin ratio values were significantly lower than in the first group before and in 120 min. after glucose loading. The second group showed average indices. Evaluation of sensitivity to insulin in 35 patients showed a decreased reaction to insulin in 17 patients, belonging mainly to the third and second groups. The blood levels of thyroxine and cortisol in these 17 patients were raised. The authors have arrived at a conclusion that the development of insulin resistance rather than the disturbed insular apparatus is likely to cause disorders in glucose tolerance in some patients with thyrotoxicosis.

[The relationship of disorders of glucose tolerance in patients with chronic hepatitis and liver cirrhosis to the severity of the pathological process]. / Zavisimost' narushenii tolerantnosti k gliukoze u bol'nykh khronicheskimi gepatitami i tsirrozom pecheni ot tiazhesti patologicheskogo protsessa.

Altogether 155 patients with different clinical types of liver lesions were examined: 73 with chronic persistent hepatitis (CPH), 39 with chronic active hepatitis (CAH), and 43 with liver cirrhosis (LC). The patients with chronic liver diseases demonstrated hyperinsulinemia and a decrease in glucose tolerance, a frequency and degree of this decrease growing with the severity of a pathological process. It is postulated taking experiments with partial hepatectomy of rats by way of example that intolerance to glucose and hyperinsulinemia is caused by partial loss of glycogen synthetic function by the liver resulting from a decrease in the number of functionally active cell elements. Experience with 8 LC patients with secondary diabetes mellitus has shown that the addition of the latter is connected with the reduction of secretory capacity of pancreatic beta-cells and with the development of relative insulin insufficiency.

[The effect of nerobol and ecdysterone on insulin-dependent processes linked normally and in insulin resistance]. / Vliianie nerobola i ékdisterona na nekotorye sviazannye insulinzavisimye protsessy v norme i pri insulinorezistentnosti.

The effect of substances with anabolic activity (metandienone and ecdysterone phytoecdysteroid) on the manifestation of insulin effects was studied on a model of insulin resistance in rats induced by injections of hydrocortisone or by insulin insufficiency caused by alloxan. The sensitivity of the body to i. v. infusion of insulin and the reactivity of isolated fatty tissue to the hormone were increased after administration of these substances to test animals. The above effects of steroids were determined by nonspecific synthesis of total proteins in cells rather than by an increase in insulin secretion.

[Insulin resistance in experimental hypo- and hyperthyroidism]. / Insulinorezistentnost' pri éksperimental'nom gipo- i gipertireoze.

The effect of thyroid hormones on the realization of body insulin function was investigated on the models of hypo- and hyperthyroidism. Hyperthyroidism resulting from thyroidectomy, caused the development of insulin resistance, expressed in a lowered body reaction to i. v. insulin infusion, a decrease in tissue sensitivity and reactivity to insulin. Insulin resistance in hypothyroidism was accountable for by a decrease in the serum total activity of insulin-like growth factors. Insulin resistance in hyperthyroidism was less notable and observed only in 10-day administration of thyroiodine; more prolonged administration of the drug (up to 30 days) restored insulin sensitivity. This effect can be accounted for by enhanced insulin independent glucose consumption caused by thyroid hormones.

[Mechanisms of insulin resistance in pregnancy]. / O mekhanizmakh insulinrezistentnosti pri beremennosti.

The causes of insulin resistance were studied in rats at late terms of pregnancy. A decrease in the sensitivity to insulin dependent incorporation of glucose in total lipids and CO2 of isolated fatty tissue of pregnant rats was shown. The maximum tissue reaction to insulin (reactivity) did not lessen indicating together with hyperinsulinemia after a glucose tolerance test and a rise of the activity of blood serum insulin-like growth factors the absence of postreceptor defects. An increase in the pregnant rats blood levels of cholesterol, triglycerides and lipoprotein atherogenic fractions was revealed. The latter in physiological concentrations made an inhibitory effect on respiration of liver and thyroid sections of intact rats. Together with the action of hormones of the fetoplacental system it was considered as one of the mechanisms of development of insulin resistance at late terms of pregnancy.

[Pathogenetic relationship between insulin resistance, insulin secretion and impaired glucose tolerance in patients with obesity]. / Patogeneticheskaia sviaz' mezhdu insulinrezistentnost'iu, sekretsiei insulina i narusheniem tolerantnosti k gliukoze u bol'nykh ozhireniem.

The distribution of obese patients without diabetes based on the results of the oral glucose tolerance test (OGTT) made it possible to define 2 groups of patients: with normal (the 1st group) and disturbed (the 2nd group) OGTT. A moderate increase in the levels of insulin and C-peptide after GTT and almost unchanged sensitivity to insulin were observed in the 1st group. A considerable increase in the levels of insulin and C-peptide after glucose intake and a considerable decrease in the sensitivity to insulin were observed in the 2nd group. In obese patients with diabetes mellitus the levels of insulin and C-peptide after the GTT were significantly lower than those in the 1st and 2nd groups. A conclusion has been made that whereas certain stages of pathogenesis of diabetes mellitus in obesity are associated with hyperinsulinemia and GTT disorder, obvious diabetes mellitus is characterized by a decrease in secretory potentialities of the insular apparatus in parallel with glucose intolerance.

[Characteristics of disorders of carbohydrate metabolism in rats with stress]. / Osobennosti narusheniia uglevodnogo obmena pri stresse.

The purpose was to study the effect of stress caused by cavitary operation (the 1st group) and stress resulting from suspending animals at the neck skin fold for 2, 4, 12 and 24 h (the 2nd group) on the development of metabolic diabetic shifts in rats. Postoperative stress was accompanied by a decrease in motor activity of rats and sispension caused intense muscular activity aimed at getting free. All elements of the diabetic syndrome expressed in glucose intolerance, reduction of sensitivity to insulin, reduced insulin action on glucose oxidation in adipose tissue, hyperinsulinemia and a rise of basal glycemia, were revealed in rats with postoperative stress; in rats of the 2nd group they were undetectable. It could be accounted for by muscular activity of animals in these groups.

[Effects of insulin in vitro in the fatty tissue of rats with alloxan diabetes after insulin treatment or administration of insulin-like growth factors from human serum]. / Effekty insulina in vitro v zhirovoi tkani krys s alloksanovym diabetom posle lecheniia insulinom ili vvedeniia insulinopodobnykh faktorov rosta syvorotki cheloveka.

Insulin insufficiency in rats caused by alloxan, results in a decrease in the sensitivity of the fatty tissue to insulin determined by glucose oxidation and synthesis of lipids manifested in a decrease in a maximum response of the tissue to insulin. Multiple injection of insulin as well as of partially purified total fraction of insulinoid growth factors causes an increase in a maximum response of the fatty tissue to insulin and a right-hand shift of dose-response curves. The total effect of the injection of insulin or partially purified growth factors is expressed in elevated sensitivity of the fatty tissue to insulin.

[The role of prostaglandins in the activation of sugar transport into the rat diaphragm]. / Uchastie prostaglandinov v aktivirovanii transporta sakharov v diafragmu krys.

Kinetic parameters of D-xylose (nonmetabolized analogue of glucose) transport were studied in isolated rat diaphragm in presence of insulin and prostaglandins E2 and F2 alpha. Prostaglandins E2 and F2 alpha simultaneously with insulin were found to increase the rate of D-xylose transport by 49 +/- 3% and 19 +/- 2%, respectively, which occurred due to increase in Vmax, while Km value of the carrier-sugar complex was unaltered.

[Glucose transport inhibition in human erythrocytes by calmodulin antagonists]. / Tormozhenie transporta gliukozy v éritrotsitakh cheloveka antagonistami kal'modulina.

Calmodulin antagonists (tryphtazin, lidocaine, dykain, palmitate) inhibit glucose transport from human erythrocytes. Glucose efflux inhibition is proportional to the concentration of antagonists in the medium and is of uncompetitive character. It is accompanied by a decrease in the maximum transport rate with the unchanged constant of dissociation in the complex: carrier-sugar. Calcium ionophores A23187 and divaleryldibenzo-18-crown-6 eliminated the inhibiting effect of pharmacological agents on glucose transport. The authors think that the glucose transport inhibition under the influence of calmodulin antagonists may be realized through the calmodulin-dependent chain inhibition under the influence of calmodulin antagonists in the carbohydrate transport system.

[Causes of hyperinsulinemia and decreased sensitivity to insulin in liver damage]. / O prichine giperinsulinemii i snizheniia chuvstvitel'nosti k insulinu pri porazheniiakh pecheni.

Chronic contamination of rats with heliotrin causing the development of hepatitis or hepatocirrhosis and partial hepatectomy to decrease the amount of liver cellular elements resulted in intolerance to glucose, a decrease in the sensitivity of the body to insulin, hyperinsulinemia after a glucose-tolerance test. The content of glycogen in the liver of the heliotrin contaminated rats was much lower than that in the controls and after glucose-tolerance an absolute increment of glycogen in the controls was 8.8-fold higher than in the heliotrin-contaminated rats. It was concluded that a decrease in glucose-tolerance and hyperinsulinemia in patients with chronic hepatitis and hepatocirrhosis were determined by a decrease in the amount of functionally active liver cellular elements and the development of insulin resistance.

[Mechanism of the increased insulin sensitivity of rats following physical training]. / O mekhanizme povysheniia chuvstvitel'nosti k insulinu u krys posle fizicheskikh trenirovok.

A rise of sensitivity to insulin was noted in healthy rats living an inactive life in a vivarium as a result of regular physical exercises (swimming with load for 30 min. during one month). It was expressed in a drop of glycemia in response to insulin administration in the presence of glycogen load, in greater glucose consumption and glycogen accumulation by tissues during incubation with insulin, in a lesser rise of C-peptide and insulin levels after glycogen load. Muscular activity was shown to incorporate glucose consumption and oxidation mechanisms unrelated to insulin regulation. Physical exercise resulted in a rise of the activity of enzymes involved in oxidation of glucose metabolism intermediate products in the presence of a decrease in the insulin level. A conclusion has been made that physical exercises determine a decrease in a demand for insulin secretion in response to a rise of the glucose level in the blood resulting in decreased insulinemia and consequently in raising sensitivity to insulin.

[Effect of adebit (N-butylbiguanide) on the metabolism and oxidation of glucose in rat tissues in vitro]. / Vliianie adebita (N-butilbiguanida) na potreblenie i okislenie gliukozy v tkaniiakh krysy in vitro.

The effect of adebit (N-butylbiguanide) on the rat tissues in vitro, namely, on sugar consumption and transport, glucose oxidation, as well as on gluconeogenesis in the rat organism, was studied. Glucose consumption and D-xylose transport in the diaphragms of intact animals and glucose consumption and oxidation in the epididymal fat of rats, given hydrocortisone, were determined. Gluconeogenesis intensity under adebit action was investigated according to the blood sugar level following adrenaline injections to rats after 24-hour fasting. It was established that the administration of adebit at concentrations of 0.2 to 0.5 mM results in intensified insulin-independent glucose consumption and xylose transport in the diaphragm, the maximum transport rate being augmented and the dissociation constant remaining unchanged. It is concluded that adebit does not change the properties of sugar transmitter, but influences the cell metabolism by inhibiting oxidative phosphorylation. The use of adebit in therapeutic concentrations (5 to 10 mcM) gave an insulin-dependent rise of glucose consumption and oxidation in the fatty tissue by 44%. A decrease in the blood sugar level in the presence of adrenaline hyperglycemia under the action of adebit therapeutic doses was not observed. It is concluded that biguanide hypoglycemizing action in diabetes mellitus is based on the biguanide potentiated insulin effectiveness.

[Sugar transport regulation in vitro by new calcium ionophores]. / Reguliatsiia transporta sakharov in vitro novymi kal'tsievymi ionoforami.

The influence of calcium ionophores--tenoyltrifluoroacetate (TTFA) and divaleryldibenzo-18-crown-6(divaleryl) on the glucose consumption, D-xylose transport and glycogen content in rat diaphragm was studied. TTFA caused a clear dose-dependent inhibition of carbohydrate transport and glycogenolysis stimulation. Divaleryl, on the other hand, raised glucose consumption, D-xylose transport without influencing glycogen content. Exclusion of Ca++ from incubation medium increased the TTFA inhibiting effect on glucose consumption, decreased its glycogenolytic effect and removed divaleryl induced stimulation of glucose transport. Mechanisms of calcium ionophore action and a possible role of intracellular Ca2+ in carbohydrate transport are discussed.

[Incidence of decreased insulin sensitivity in obese patients]. / Issledovanie chastoty snizheniia chuvstvitel'nosti k insulinu u bol'nykh ozhireniem.

A method has been presented for the detection of organism sensitivity to insulin, involving simultaneous administration of insulin (intravenously) and the solution of partially hydrolized starch (orally), followed by the determination of the blood sugar level after 1 and 2 hours. By means of this method sensitivity to insulin was established in 55 patients with obesity and 16 healthy humans. It was found that sensitivity to insulin among patients with obesity of the I-III stages is lowered in 33% of cases and in subjects with the IV stage of the disease in 62%. The results of the determination of sensitivity to exogenous insulin correlate with IRI level in these patients.

[Decreased tissue sensitivity to insulin in rats after hydrocortisone or indomethacin administration: the association with prostaglandin action]. / Snizhenie tkanevoi chuvstvitel'nosti insulinu u krys posle vvedeniia gidrokortizona ili indometatsina, sviaz's s deistviem prostaglandinov.

Hydrocortisone or indomethacin injection to rats induces insulin hyposensitivity determined by the glycemic curve after insulin injection and by the glycogen content in the diaphragm and gastrocnemius muscle following incubation of these tissues with glucose and insulin. It is suggested that the effect of the drugs is caused by their ability to inhibit the biosynthesis of prostaglandins, which enhance the rate of glucose transport to cells. To study this problem to diaphragmatic and uterine tissues of healthy rats were incubated with prostaglandins E2 or F2 alpha in the presence of insulin and glucose. An increase in the tissue glucose absorption from the medium was observed under prostaglandin action. Therefore, one of the reasons for a decrease of the tissue sensitivity to insulin may lie in the inhibited prostaglandin biosynthesis in the tissues.