Growth hormone and carbohydrate metabolism in myocardial infarct]

The indices of somatotropin were determined in myocardial infarction patients by means of immunological techniques, and those of blood sugar by the Hagedorn--Jensen technique. Single growth hormone determinations were conducted in 40 myocardial infarction patients, aged 45 to 80 years, with different periods from the onset of the disease. In 23 patients the somatotropin and blood sugar indices were studied dynamically on the 1st--3rd and 7th--10th days of the infarction. An equal number of patients was subjected on the 28th--30th day of the disease to determinations of growth hormones secretion in conjunction with the glucose-tolerance test (on an empty stomach, and 1 and 3 hours following the administration of 100 g of glucose). The conducted investigation demonstrates that single determinations of somatotropin fail to give grounds for conclusions as to its secretion due to the wide individual variations of this parameter. The dynamics of somatotropin content depends on the severity of the myocardial infarction in the given patient and does not correlate with the changes in the blood sugar level. Five types of somatotropin secretion were distinguished with the glucose-tolerance test. Patients with decreased tolerance of the carbohydrates tend to have a torpid and perverted types of somatotropin secretion.     

Effect of cogent db,a herbal drug,on plasma insulin and hepatic enzymes of glucose metabolism in experimental diabetes

Aims: The present study was designed to investigate the effect of cogent db, a polyherbal drug on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats.
Methods: Male Wistar rats body weight of 180–200 g (six normal and 18 diabetic rats) were used in this study. The rats were divided into four groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group: Group 1, normal rats given 2 ml of saline; Group 2, diabetic control rats given 2 ml of saline; Group 3, diabetic rats given aqueous solution of cogent db (0.45 g/body kg weight); and Group 4, diabetic rats given aqueous solution of glibenclamide (600 µg/kg body weight). The treatment was given for 40 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals.
Results: Treatment with cogent db resulted in a significant reduction in blood glucose and the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity were significantly increased in alloxan-diabetic rats.
Conclusions: The present investigation suggests that cogent db controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible because it regulates the activities of hepatic glucose metabolic enzymes.     

Antidiabetic effect of diasulin, a herbal drug, on blood glucose, plasma insulin and hepatic enzymes of glucose metabolism in hyperglycaemic rats

AIM: The present study was designed to investigate the effect of diasulin, a polyherbal drug, on blood glucose, plasma insulin and the activities of hepatic glucose metabolic enzymes in alloxan-induced diabetic rats. METHODS: Male Wistar rats, body weight of 180-200 g (12 normal and 30 diabetic rats), were used in this study. The rats were divided into seven groups after the induction of alloxan diabetes. In the experiment, six rats were used in each group. Group 1: normal rats given 2 ml of saline; group 2: normal rats given aqueous solution of diasulin (0.20 g/kg of body weight); group 3: diabetic control rats given 2 ml of saline; group 4: diabetic rats given aqueous solution of diasulin (0.05 g/kg of body weight); group 5: diabetic rats given aqueous solution of diasulin (0.10 g/kg of body weight); group 6: diabetic rats given aqueous solution of diasulin (0.20 g/kg of body weight) and group 7: diabetic rats given aqueous solution of glibenclamide (600 micro g/kg of body weight). The treatment was given for 30 days. After the treatment, fasting blood glucose, plasma insulin, urine sugar and the activities of hepatic glucose metabolic enzymes were determined in normal and experimental animals. RESULTS: Treatment with diasulin resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in plasma insulin and total haemoglobin and a significant improvement in glucose tolerance. Diasulin also resulted in a significant reduction in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase in the liver, whereas the level of plasma insulin and hepatic hexokinase activity was significantly increased in alloxan diabetic rats. CONCLUSIONS: The present investigation suggests that diasulin, a polyherbal drug, controls the blood glucose level by increasing glycolysis and decreasing gluconeogenesis with a lower demand of pancreatic insulin than in untreated rats. This is possible, because it regulates the activities of hepatic glucose metabolic enzymes.     

Fat storage is partially dependent on vagal activity and insulin secretion of hypothalamic obese rat

Hypothalamic MSG-obese rats show hyperinsulinemia and tissue insulin resistance, and they display intense parasympathetic activity. Current analysis investigates whether early subdiaphragmatic vagotomy prevents tissue insulin sensitivity impairment in adult obese MSG-rats. Hypothalamic obesity was induced by MSG (4 mg/g BW), daily, from birth up to 5 days. Control animals receiving saline solution. On the 30th day rats underwent bilateral subdiaphragmatic vagotomy or sham surgery. An intravenous glucose tolerance test (ivGTT) was performed when rats turned 90 days old. Total white fat tissue (WAT) from rat carcass was extracted and isolated; the interscapular brown fat tissue (IBAT) was weighed. Rather than blocking obesity, vagotomy reduced WAT and IBAT in MSG-obese rats when the latter were compared to sham MSG-rats. High blood fasting insulin and normal glucose levels were also observed in MSG-obese rats. Although glucose intolerance, high insulin secretion, and significant insulin resistance were recorded, vagotomy improved fasting insulinemia, glucose tolerance and insulin tissue sensitivity in MSG-obese rats. Results suggest that increased fat accumulation is caused, at least in part, by high blood insulin concentration, and enhanced parasympathetic activity on MSG-obese rats.     

Content of sugar and immunoreactive insulin in the blood of patients with myocardial infarct]

The content of sugar in the blood and that of immunoreactive insulin was determined in myocardial infarction cases on the 1st, 7th and 30th day. On the 30th day the carbohydrates tolerance test was conducted, and the content of immunoreactive insulin was determined after a glucose provocation. The assessment of glycemia and of the content of immunoreactive insulin was made in accordance with the type of the sugar curve. Hyperglycemia during the acute period of myocardial infarction was detected in 1/3 of the patients, a decrease of carbohydrates tolerance--2/3. Transient hyperglycemia was observed in persons in whom the glycemic and insulinemic curves resembled those in diabetes mellitus. The patients of this group displayed the same symptoms as those with diabetes mellitus. The dynamics of the content of the immunoreactive insulin from day to day of the disease differed in patients with transient hyperglycemia from those with normoglycemia.     

Insulin mimetic effects of macrocyclic binuclear oxovanadium complexes on streptozotocin-induced experimental diabetes in rats

Aim:  The vanadium complexes so far tested for their insulin mimetic effects are either mono- or binuclear and contain only acyclic ligands. The leaching or hydrolysis of vanadyl ions from these complexes is much easier, and hence they elicit side effects. In the present study, a new binuclear macrocyclic oxovanadium complex was synthesized, and its efficacy was studied on streptozotocin (STZ)-induced diabetic rats over a period of 30 days.
Methods:  The insulin mimetic effect of the complex was tested on the blood sugar level in the STZ-diabetic rats and on the activities of the carbohydrate-metabolizing enzymes present in the liver.
Results:  Administration of vanadium complex to STZ-induced diabetic rats decreased blood glucose levels from hyperglycaemic to normoglycaemic when compared to diabetic rats. The activity of carbohydrate-metabolizing enzymes such as hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen content were increased to near normal in vanadium complex-administered diabetic rats. The biochemical studies such as assay of blood urea and glutamate oxaloacetate transaminases revealed that the complex is not toxic to the system.
Conclusion:  The nontoxic nature of this complex may be due to the presence of the vanadyl ions in an intact macrocyclic form. Further, the vanadyl ions present in the macrocyclic binuclear oxovanadium complex are very close to each other, and this may enhance the insulin mimetic activity by synergic effect.     

The effect of oral synthetic protease inhibitor (FOY 305) on endocrine pancreas and carbohydrate and lipid metabolism in normal and streptozotocin-induced diabetic rats

The effect of long-term oral synthetic protease inhibitor (FOY 305) administration on fasting blood sugar (FBS), body weight, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, hepatic enzyme activities, and plasma lipids in normal and streptozotocin (STZ)-induced diabetic rats was studied. Normal rats treated with oral FOY 305 for 9 weeks were found to have pancreatic hypertrophy and decreased body weight gain as compared with the untreated normal controls. FBS, glucose tolerance, plasma insulin and glucagon levels, pancreatic insulin and glucagon contents, and plasma lipids were uninfluenced in FOY 305 treated normal rats. STZ-induced diabetic rats treated with oral FOY 305 were found to have decreased FBS for 5 weeks after the beginning of FOY 305 administration as compared with the untreated diabetic controls, whereas at the 7th and 9th week after treatment there was no difference in FBS between FOY 305 treated and untreated diabetic rats. In the metabolic balance observed at the 4th week after treatment, a slight improvement of the diabetic state was found in FOY 305 treated diabetic rats. There was no apparent difference in the blood sugar curve and insulin response following oral glucose load between diabetic rats treated for 7 weeks and untreated diabetic rats. All the rats were sacrificed after 9 weeks of treatment. Diabetic rats treated with oral FOY 305 for 9 weeks showed pancreatic hypertrophy and decreased plasma glucagon level and decreased pancreatic glucagon content as compared with the untreated diabetic controls, whereas there was no difference in body weight, plasma insulin level and pancreatic insulin content between FOY 305 treated and untreated diabetic rats. Furthermore, oral FOY 305 treatment improved hyperlipidemia in STZ-induced diabetic rats and also significantly improved the hepatic pyruvate kinase and phosphoenlpyruvate carboxykinase activities of diabetic rats. These improvements might partly be due to a decreased pancreatic content and secretion of glucagon and/or a direct action of the synthetic PI, FOY 305 to tissues.     

Comparative data on the radioimmunological and biological activity of luteinizing hormone in the pituitary gland and the blood serum of human fetuses

Determination of immunoreactive luteinizing hormone (LH) was carried out in 291 hypophyses of 8--34-week human fetuses, and in 92 blood serum samples of 14--34 week human fetuses. Immunoreactive LH was revealed in human hypophyses as soon as the 8th week of embryogenesis. In female fetuses the concentration and content of the hormone showed a sharp rise from the 14th--16th to the 19th--20th week. The LH concentration displayed a gradual decrease and the hormone content remained at the same level from the 21st--22nd to the 32nd--34th week. The LH concentration and content showed practically no change in male fetuses from the 14th--16th to the 23rd--24th week. A sharp elevation of the hormone level was observed from the 23rd--24th to the 27th--28th week. Immunoreactive LH was revealed in the blood of human fetuses from the 14th to the 34th week. The LH concentration was significantly greater from the 21st--22nd and 23rd--24th weeks in female than in male fetuses. In comparing the data obtained as a result of application of radioimmunological and biological methods there was revealed a coincidence of the time of appearance, of the changes and of the sex differences in the immunoreactive LH level and its biological activity in the hypophysis and in the blood of human fetuses.     

Expression of yeast hexokinase in pancreatic beta cells of transgenic mice reduces blood glucose, enhances insulin secretion, and decreases diabetes.

It has been proposed that endogenous hexokinases of the pancreatic beta cell control the rate of glucose-stimulated insulin secretion and that genetic defects that reduce beta-cell hexokinase activity may lead to diabetes. To test these hypotheses, we have produced transgenic mice that have a 2-fold increase in hexokinase activity specific to the pancreatic beta cell. This increase was sufficient to significantly augment glucose-stimulated insulin secretion of isolated pancreatic islets, increase serum insulin levels in vivo, and lower the blood glucose levels of transgenic mice by 20-50% below control levels. Elevation of hexokinase activity also significantly reduced blood glucose levels of diabetic mice. These results confirm the role of beta-cell hexokinase activity in the regulation of insulin secretion and glucose homeostasis. They also provide strong support for the proposal that reductions in beta-cell hexokinase activity can produce diabetes.     

Effect of the administration of prednisolone, glucose and insulin during early postnatal ontogenesis on indices of carbohydrate and lipid metabolism in the adult rat

To clear out the role of early postnatal exposures in the formation of glycemic homeostasis in adult rats receiving pharmacological doses of glucocorticoids, glucose (G) or insulin (I) in the early postnatal period (starting from the 2d-8th day) indices of their carbohydrate-fat metabolism were studied. The results of these exposures were assessed by the content of 11-oxy-corticosteroids, immunoreactive insulin (IRI), glucose (G), urea and free fat acids (FFA), in the blood; by the glucose tolerance test and the animals' resistance to the diabetogenic affect of alloxan. It was shown that in all the experimental series the IRI level in the blood of the adult animals was lowered. The administration of G or glucocorticoids in the early postnatal period resulted in a decrease in the G concentration and an elevation of the FFA level in the blood, time-legged recovery of the G level in the blood up to the initial values in the glucose tolerance test in the adult animals. Glycemic load in the 1st week of the life of newborn rats increased adult animals' tolerance to the diabetogenic effect of alloxan.     

胎鼠胰腺干细胞体外对胰岛的保护作用观察

目的观察胎鼠胰腺干细胞体外对胰岛功能的保护作用。方法将孕16d的sD大鼠胎鼠胰腺干细胞分离、纯化、培养传代,免疫细胞化学法及流式细胞术鉴定;分离纯化sD大鼠胰岛,双硫腙鉴定后分为A组和B组,分别行单纯胰岛培养及胰岛与胰腺干细胞联合培养14d,期间观察胰岛形态变化、检测胰岛存活率及细胞凋亡率,ELISA法检测胰岛素分泌量、计算刺激指数。取两组培养7d后悬浮生长的胰岛移植入糖尿病大鼠左肾包膜下,术后每天尾静脉采血以快速血糖测试仪检测血糖。结果胎鼠胰腺干细胞培养传代3代后免疫细胞化学可见巢蛋白（Nestin）阳性细胞,流式细胞术测定其含量占74．1％;培养第7、14天时B组胰岛存活率显著高于A组（P均〈0．01）,培养第7天时B组胰岛细胞凋亡率显著低于A组（P〈0．05）;培养第7、14天时B组高糖刺激后胰岛素分泌量及刺激指数均显著高于A组（P均〈0．01）;B组移植后大鼠血糖第5天降至正常。结论胎鼠胰腺干细胞与胰岛联合培养可明显延长胰岛体外存活时间并使其保持良好的活性。     

Content of immunoreactive insulin and catecholamines in blood plasma and disorders of carbohydrate metabolism in patients with myocardial infarct]

The blood plasma level of immunoreactive insulin was studied dynamically be means of radioimmunoassay and the blood sugar level by the orthotoluidine technique in 70 patients with large-focal myocardial. In 48 of them the plasma level of catecholamines was determined simultaneously by the fluorimetric technique. The control group of patients was composed of ischaemic heart disease cases without myocardial infarction. Patients with acute myocardial infarction appeared to have hypercatecholaminemia and insufficient insulin excretion: 65.4% of acute myocardial infarction patients having an absolute insulin insufficiency, and 34.6% -- a relative one. The most distinct hypercatecholaminemia and insulin secretion inhibition were observed in those with acute myocardial infarction and congestive heart failure. In patients with an absolute insulin insufficiency the plasma level of noradrenaline was considerably and statistically significantly higher, than in those with a relative insulin insufficiency. In patients with high hypercatecholaminemia the insulin secretion inhibition was noted more often and was more severe. In patients with acute myocardial infarction and an absolute insulin insufficiency complications, such as congestive heart failure and rhythm and conductivity disorders, were more frequent and lasting, than in those with a relative insulin insufficiency. During the acute period of myocardial infarction the disorders in the carbohydrate metabolism were observed in 82.2% of the cases, and were more distinct in those with an absolute insulin insufficiency. By the 20th--22nd postinfarction day the carbohydate metabolism disorders persisted in 35% of the myocardial infarction patients.     

Effect of clonidine on glucose, insulin and glucagon responses to a protein meal in type 2 diabetics

The authors investigated the effects of clonidine (alpha-2 stimulating agent) on blood glucose, insulin and glucagon levels in order to assess the alpha-adrenergic regulation of endocrine pancreatic secretion. Ten hypertensive female subjects affected with type 2 diabetes were studied; each subject was given a protein meal (boiled beef 200 g); blood samples were taken at -30, 0, 30, 60, 90 and 120 min; after this test each subject was treated for 4 days with clonidine (0.150 mg, 3 times/day per os); at the 5th day the protein meal was repeated under the same conditions except for the added administration of clonidine. Plasma glucose, insulin and glucagon were estimated. The administration of a protein meal caused a significant increase of blood glucose (peak at 60 min), insulin (peak at 90 min) and glucagon (peak at 90 min) levels; the association of clonidine caused an increase of blood glucose (single values and total areas) without changes of insulin and glucagon levels, when compared to those obtained before clonidine treatment. In conclusion, the association of clonidine to a protein meal caused impaired glucose tolerance presumably due to a direct glycogenolytic effect, occurring in the liver on account of an alpha-2 receptor stimulation, insulin and glucagon not being involved in this phenomenon.     

Voluntary running improves glucose tolerance and insulin resistance in female spontaneously hypertensive rats

We evaluated the effects of voluntary exercise training on glucose metabolism and measures of insulin sensitivity in female spontaneously hypertensive rats (SHR). Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls. Exercising SHR were housed in running wheels for 8 weeks (SHRx8) or 16 weeks (SHRx16). At 22 weeks of age, we measured systolic blood pressure, performed oral glucose tolerance tests, and determined hexokinase activity and glucose transporter (GLUT) 4 content in skeletal muscle to assess intracellular glucose metabolism. Blood pressure was lower in WKY (139 ± 12 mm Hg) than untrained SHR (216 ± 13 mm Hg). Exercise training caused a reduction in blood pressure (−18 mm Hg) for SHRx8. After a brief (5-h) fast, serum glucose was lower in SHR that exercised compared with sedentary SHR, whereas insulin concentrations were identical between all SHR and WKY. Corresponding free fatty acids (FFA) were twofold higher in SHR than in WKY. In response to glucose, SHR demonstrated higher glucose and FFA responses, with exercise decreasing the glucose values in a dose-dependent manner. Although the insulin response was comparable in all groups, the glucose-to-insulin ratio was higher in SHR, indicating a relative insulin resistance for both glucose disposal and suppression of free fatty acids. Hexokinase activity and GLUT4 content were elevated 1.4- and 2.8-fold, respectively, in plantaris muscle of SHRx16, suggesting an improvement in the capacity for glucose transport and phosphorylation with exercise. These results provide evidence that voluntary running in female SHR lowers blood pressure and selectively increases glucose uptake and insulin action, but not suppression of FFA.     

The effect of hypophysectomy on the function of the insulin-sensitive central nervous system glucoregulator receptor.

Hypophysectomized and healthy control rats were studied to investigate the mechanism of action of the insulin-sensitive glucoregulator receptor of the central nervous system (CNS). Glucagon-free insulin (500 muU) was injected into the carotid artery, and the peripheral blood glucose was monitored. An immediate significant fall in the blood sugar was observed in intact as well as in hypophysectomized rats. To control these experiments buffer was injected into the carotid artery, or 500 muU insulin was given through the jugular vein of intact and hypophysectomized animals. The systemic blood sugar level remained unchanged for 10-15 min in the control experiments. The results indicate that the function of this insulin-sensitive glucoregulator CNS receptor is not impaired in the hypophysectomized state. The initial phase of its effect, the sudden decrease of the blood sugar level, appears to be independent of pituitary hormone secretion.     

Effect of certain antibiotics of tetracycline series on the level of blood sugar and the role of insulin in the mechanism of its regulation]

Experiments on male rats showed enterally administered tetracycline and chlortetracycline to promote an elevation of the blood sugar level. These antibiotics administered once together with glucose retarded the normalization of the blood sugar concentration. After 7-day administration of tetracycline and chlortetracycline glucose load caused a stable hyperglycemia. Special experiments with depancreatization and insulin injection to the animals and also the intravenous injection of glucose and the antibiotic demonstrated that the changes in the blood sugar concentration under the effect of tetracycline were associated both with its inhibitory action on the absorbing function of the intestine and with the retarded glucose utilization in the tissues. Insulin injected intramuscularly eliminated the hyperglycemic effect caused by the antibiotics.     

Sex steroids deficiency impairs glucose transporter 4 expression and its translocation through defective Akt phosphorylation in target tissues of adult male rat

There is a substantial body of evidence suggesting that altered level of sex steroids in male is associated with insulin resistance and type 2 diabetes mellitus. However, the mechanism of this effect is not apparent. Our recent study indicated that testosterone deprivation decreases insulin receptor expression and glucose oxidation in insulin target tissues. The present study was designed to assess the impact of deficiency of testosterone and estradiol on Akt phosphorylation, glucose transporter expression, and glucose uptake in skeletal muscle, adipose tissue, and liver of adult male rat. Adult male albino rats of Wistar strain were orchidectomized and supplemented with testosterone (100 μg/100 g body weight per day), estradiol (5 μg/100 g body weight per day), and their combination (100 μg testosterone plus 5 μg estradiol per 100 g body weight per day) for 15 days from the 11th day postorchidectomy. On the day after the last treatment, animals were perfused; and blood was collected for the assay of plasma glucose, serum insulin, testosterone, and estradiol. Gastrocnemius muscle, adipose tissue, and liver were dissected out and used for the assay of various parameters such as Akt phosphorylation, glucose transporter (GLUT) 2 and 4 expression, glucose uptake, and glycogenic and glycogenolytic enzymes activity. Castration elevated the blood glucose level, which was accompanied by inhibitory effect on serum insulin, Akt phosphorylation, GLUT4 expression and its plasma membrane population, glucose uptake, glycogen and glycogen synthase activity, and stimulatory effect on GLUT2 expression and glycogen phosphorylase activity in tissues studied. After testosterone and its combination with estradiol supplementation to castrated rats, a normal pattern of all these parameters was restored. Estradiol administration to castrated rats increased the Akt phosphorylation without altering other parameters studied. It is concluded from the present study that sex steroids deficiency–induced defective glucose uptake in skeletal muscle and adipose tissue is mediated through defective Akt phosphorylation and GLUT4 expression in plasma membrane.     

Effect of troglitazone on vascular and glucose metabolic actions of insulin in high-sucrose-fed rats

In rats, diets high in simple sugar induce insulin resistance and alter vascular reactivity. The present study was designed to evaluate the effects of 5 weeks treatment with troglitazone on insulin sensitivity, regional hemodynamics, and vascular responses to insulin in chow-fed and high-sucrose-fed rats. Male rats were randomly divided in 4 groups to receive a regular chow diet in the absence (group 1) or presence of troglitazone (0.2% in food; group 2), or a sucrose-enriched diet in the absence (group 3) or presence of troglitazone (group 4) for 5 weeks. The rats were instrumented with Doppler flow probes and intravascular catheters to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Glucose transport activity was examined in isolated muscles. Sucrose feeding was found to induce insulin resistance and to impair the insulin-mediated skeletal muscle vasodilation. Treatment with troglitazone was found to increase whole-body insulin sensitivity in sucrose- and chow-fed rats, but had no effect on skeletal muscle glucose transport activity measured in isolated muscles from both dietary groups. Changes in regional hemodynamics were observed in both dietary cohorts treated with troglitazone, and the hindquarter vasoconstrictor response to insulin noted in sucrose-fed rats was abolished by the treatment. The vascular effects of troglitazone, and its insulin-related attenuating effects on contractile tone, could have contributed, in part, to improve insulin action on peripheral glucose disposal, presumably by improving blood flow distribution and glucose delivery.     

Prevention of hypertension,hyperglycemia and vascular oxidative stress by aspirin treatment in chronically glucose-fed rats

OBJECTIVES : To examine whether an in vivo chronic treatment with aspirin could prevent insulin resistance, oxidative stress and blood pressure elevation associated with high glucose feeding in rats. METHODS : Sprague-Dawley rats (SD) were given a normal chow diet for 3 weeks combined or not with a 10% glucose drinking solution with or without aspirin added to their drinking water, and were compared to control SD rats which received normal chow and tap water to drink for 3 weeks. Oxidative stress was evaluated by measuring superoxide anion (O2-) production in the aorta using the lucigenin-enhanced chemiluminescence method. Antioxidant reserve was assessed by measuring the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) in the blood. Fasting blood sugar and insulin levels were measured at the end of the study. RESULTS : The systolic blood pressure (SBP), the aortic basal superoxide production, plasma levels of insulin and glucose, as well as the insulin resistance index, were all significantly higher in rats fed glucose for 3 weeks, compared to control rats. The simultaneous treatment with aspirin prevented the increase in SBP, in plasma glucose levels and in aortic O2- production, and attenuated the rise in insulin levels as well as insulin resistance in the glucose-fed rats. Positive correlations between aortic O2- production and SBP, as well as between insulin resistance and SBP or between O2- production and insulin resistance, were found in control, glucose-fed and aspirin-treated, glucose-fed rats. The activities of GPx and SOD in the erythrocytes did not differ in the three groups. An increase in plasma SOD activity was observed in glucose-fed rats. CONCLUSIONS : Chronic in vivo treatment with aspirin prevented the development of hypertension and reduced insulin resistance significantly in chronically glucose-fed rats. Aspirin seems to produce these effects through its antioxidative properties, since it was found to prevent the increase in aortic O2- production observed in chronically glucose-fed rats.     

The effect of different kinds of refeeding on islet glucose phosphorylating activities

The aim of the present work has been to study the regulating effect of different kinds of diet on the activities of enzymes that phosphorylates glucose into glucose 6 phosphate in the islets of Langerhans. The metabolism of glucose in the B cell is controlled by two different enzymes, hexokinase and glucokinase, whose activities are lowered during fasting; this coincides with lowered levels of blood glucose and blood insulin and with a blocking of the insulin-secretory response toward glucose. Refeeding with a high-carbohydrate diet restores glucokinase activity in islet extracts, blood insulin, and blood glucose. By contrast, refeeding with a low-carbohydrate diet restores hexokinase activity in islet extracts, restores poorly blood insulin, and is unable to unblock the insulin secretory response toward glucose. These results support the important role that glucokinase plays in the regulation of glycolytic flux and on insulin secretion in the B cell. Hexokinase could play a role in the regulation of the glycolytic flux when the B cell responds to other secretagogues.