Beneficial effect of vitamin E on the metabolic parameters of diabetic rats

The role of vitamin E in the pathogenesis of diabetes mellitus is unknown. The purpose of this study was to examine the effect of oral administration of vitamin E on some of the metabolic parameters of experimental diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (60 mg/kg body weight at 12 weeks of age). Vitamin E (0.2, 0.4, 0.8 mg/kg body weight) was administered orally for a period of 3 weeks to normal and diabetic Wistar rats. In some experiments, Vitamin E was given either before or after the induction of diabetes mellitus. Blood glucose level and weight were recorded for each rat in different groups on a weekly basis. Oral glucose tolerance test (OGTT) was performed on fasted normal, diabetic and vitamin E treated rats at the end of the experiment. Vitamin E significantly (p < 0.01) reduced blood glucose levels in experimental diabetes mellitus at all doses as compared to untreated rats. Vitamin E induced weight loss in normal as well as in diabetic rats. The beneficial effect of vitamin E on the hyperglycaemia of diabetic rats was dose-dependent. Moreover, vitamin E also improved OGTT in diabetic rats compared to untreated diabetics. In conclusion, vitamin E may play a role in glucose metabolism and thus be a useful adjuvant therapy in type I diabetes. (Mol Cell Biochem 261: 35–42, 2004)     

Independent influence of insulin, catecholamines, and thyroid hormones on metabolic syndrome

The objective of this study was to examine whether metabolic syndrome, defined according to adult treatment panel III criteria, is associated with insulin, catecholamines, and thyroid hormones, independently of age and gender. A cohort of 651 euthyroid overweight and obese patients, 440 women and 211 men, aged 18-68 years, were examined. Central fat accumulation (indirectly measured by waist circumference), fasting thyroid-stimulating hormone (TSH), FT(3), FT(4), insulin, glucose, and lipid (cholesterol, HDL-cholesterol, and triglyceride) serum concentrations, 24-h urinary catecholamines, and the level of insulin resistance (estimated by homeostasis model assessment for insulin resistance (HOMA(IR))) were measured. Patients with metabolic syndrome showed higher insulin (P < 0.001) and FT(3) (P < 0.001) serum levels and higher 24-h urinary noradrenaline (P < 0.001) than subjects without this syndrome. The number of metabolic syndrome parameters was directly associated with insulin (P < 0.001) and FT(3) (P < 0.05) serum levels, and with 24-h urinary noradrenaline (P < 0.001) in the whole population. When a multiple regression analysis was performed with the metabolic syndrome as the dependent variable, and age, gender, and insulin, and TSH, FT(3), FT(4) serum levels, and 24-h urinary noradrenaline and adrenaline as independent variables, the metabolic syndrome maintained an independent positive association with age (P < 0.001), male sex (P < 0.001), insulin (P < 0.001), and 24-h urinary noradrenaline (P < 0.001). In conclusion, this study suggests that insulin and noradrenaline cooperate independently to the development of the metabolic syndrome.     

Effect of thyroid hormones on the levels of metabolic intermediates in diabetic rat liver

Experimental diabetes results in an inhibition of the glycolytic and lipogenic pathways in rat liver, while treatment of diabetic rats with T3 for four days increases the activity of a number of enzymes linked to lipogenesis. Hepatic metabolites were estimated in control (untreated), control + T3-treated, alloxan-diabetic and alloxan-diabetic + T3-treated rats. Diabetes resulted in the expected decrease in the content of fructose 2,6-bisphosphate and an increase in the content of cyclic AMP and citrate, changes consistent with an inhibition of hepatic glycolysis. Treatment of diabetic rats with T3 did not reverse these changes. There was a marked accumulation of both acetyl CoA and citrate in the diabetic rat liver, which was of even greater magnitude in diabetic and in the T3-treated group. In addition, T3 treatment significantly increased the free CoA content of liver in both normal and diabetic groups. Of the parameters measured which influence lipogenesis, including long chain acyl CoA, the energy charge and redox state of the nicotinamide nucleotides, the raised hepatic citrate content correlated most closely with the known increase in lipogenesis in diabetic rats treated with T3 for a four day period.     

Role of insulin and counter-regulatory hormones in the metabolic changes caused by insulin deprivation in diabetic patients

In eight insulin dependent diabetic patients treated by continuous subcutaneous insulin infusion (1.1 +/- 0.2 U/h), the levels (measured hourly from 23 h to 05 h) of blood glucose, non esterified fatty acids (NEFA), glycerol and 3-OH-butyrate (3-OH-B) have been correlated to the circulating levels of free insulin (FIRI), glucagon, growth hormone or cortisol, in two experimental conditions: A. Insulin being infused as usual (physiological FIRI levels) and B. Progressively declining FIRI levels (insulin infusion arrested at 23 h). In condition A, blood glucose levels correlated significantly to both insulin and glucagon; NEFA, glycerol and 3OH-B correlated only to insulin. In condition B, blood glucose was significantly correlated to insulin but not to glucagon while NEFA, glycerol and 3-OH-B were significantly correlated to both hormones but not to growth hormone or cortisol. Therefore, on the metabolic deterioration that follows insulin withdrawal, growth hormone and cortisol seem to play a minor role, the main role being played by the decrease in circulating insulin levels and to a lesser extent by the increase in glucagon levels.     

Circadian oscillations of thyroid hormones and insulin in the serum of fasting rats

Adult male Wistar rats adapted to a 12:12 h light:dark regimen, fed or after a 24- or 48-h fast, were decapitated at 3-h intervals during a single day. They were deprived of food at day-time intervals ensuring that on decapitation they had fasted for the same length of time, i.e. 24 or 48 h. Thyroid hormones, insulin and glucose concentrations were determined in their serum. Fasting did not significantly affect circadian thyroxine, triiodothyronine and reverse triiodothyronine rhythms compared with the findings in fed animals; 24, but not 48 hours' fasting led to a shift in the acrophase of circadian insulin and glucose oscillations compared with fed rats. The maintenance of original circadian thyroid hormones and insulin rhythm in rats which fasted for short lengths of time testifies to a dependence of the stimulus on the time of day.     

The effect of insulin on delayed augmented mast-cell mediated mitogenesis in diabetic rats

Delayed augmented mitogenic reactivity follows mast-cell secretion in mesentery and skin in streptozotocin-diabetic rats with 4-week insulin-deficiency (Norrby 1982; Norrby et al. 1982; Norrby 1983). In such rats the basal proliferation is essentially unchanged in the mesentery and skin, whereas it is significantly increased in the small gut and significantly decreased in the kidney. On treating rats with 4-week-old diabetes with very-long-acting insulin for over 3 days (16 U/kg X 2 daily) the basal proliferation of the small gut and the kidney apparently became normal, the body weight increased, and the blood glucose concentration dropped substantially and progressively. However, insulin-treatment did not affect the mast-cell-dependent mitogenesis in the mesentery following intraperitoneal injection of the mast-cell secretagogue compound 48/80, as judged by specific DNA activity and mitosis counting. We conclude that some metabolic or cellular feature of diabetes which is not restored by 3-day insulin treatment, and not insulin deficiency itself, is the cause of the delayed increased mitogenic reactivity that follows mast-cell secretion in diabetic rat.     

Circadian oscillations of thyroid hormones, insulin and glucagon in the blood of laboratory rats in the course of the year

The concentration of thyroid hormones and insulin in the serum that of glucagon in the plasma and glucose in the blood was determined at 3-hour intervals, in the course of one day, at different times of the year, in adult male rats (Wistar strain) of a conventional breed kept under standard conditions with a 12:12 h light:dark regimen. The lowest thyroid hormone and glucagon concentrations and the highest insulin and blood glucose levels were found in the winter. In various seasons, circadian oscillations of the thyroid hormones culminated in the dark part of the day and that of glucagon in the light part, with the exception of the autumn. Circadian oscillation of insulin levels culminated at different times of day during the year. The pronounced changes found in the examined hormones in the laboratory rat at various times of the year are evidently the outcome of adaptation to changes in external environmental conditions during phylogenesis. In the polarity of changes in these indicators between the winter and the summer or the spring, the laboratory rat bears the closest resemblance to wild mammals.     

Rat brain insulin degrading enzyme in insulin and thyroid hormones imbalances

Rat brain insulin degrading enzyme activity and its relationship with insulin receptor were investigated in experimental hyperglycemia, hyperinsulinemia, hypothyroidism and hyperthyroidism. Insulin degrading enzyme activity was assessed in synaptosomes and high speed cytosol using [125I]insulin. Levels of insulin degrading enzyme were changed in high speed cytosol in insulin and thyroid hormone imbalances. These results suggest that insulin degrading enzyme in brain is predominantly active in cytosol and is subject to regulation by insulin and thyroid hormones. Probably it plays some role in long term effects of insulin in brain.     

Effects of Ballota nigra on blood biochemical parameters and insulin in albino rats

Ingestion of aqueous 70% ethanol extract of Ballota nigra (400 mg/kg body weight for 7 days) by albino rats (n=10) was investigated to study its effects on glucose, total cholesterol, triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), troponin I (TnI), serum creatine kinase (CK), total protein, total bilirubin and blood urea. Ballota nigra extract caused a significant decrease in blood glucose, total serum cholesterol and CK levels. Blood levels of TnI, AST, ALT, triglycerides, total bilirubin, total protein and blood urea were unchanged. The hypoglycemic effect of Ballota nigra extract on albino rats was further investigated by conducting a glucose tolerance test intraperitoneally (IPGTT). Healthy rats that were fasting for 18 hours followed by administration of a dose of 400 mg/kg body weight of the crude extract of Ballota nigra, orally. A significant decrease in blood glucose levels (after 15, 30, and 45 minutes) with a significant increase in serum insulin level (after 15 and 30 minute) was noted. These results suggest that, the crude extract of Ballota nigra have hypoglycemic, insulin-releasing and cholesterol lowering effects in rats.     

Relaxing effect of insulin in renal arteries from diabetic rats

Abnormal renal vasomotor tone exists in the early stages of diabetes mellitus. Insulin has been proposed to modulate renal function and to possess vasodilatory effects. The present study was initiated in order to evaluate the direct effect of insulin on isolated renal arteries. Twelve insulin-treated streptozotocine diabetic rats with diabetes for 50 days were compared with 15 weight-matched control rats. The contractile responses to 60 mM K+ and 10(-4) M noradrenaline, and the insulin- (0.8-6.4 I.U./ml) induced relaxation of vessels precontracted with noradrenaline, were similar in diabetic and control rats. There was a tendency towards greater relaxation in diabetic (71%) than in control rats (54%). Nw-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) given before noradrenaline tended to attenuate the insulin-induced relaxation, while addition of L-arginine (10(-6) M) to L-NAME attenuated the relaxation in diabetic but increased it in control rats (P < 0.05). The effect of insulin was tested further in control rats and was not influenced by administration of a single dose (10(-6) M) of indomethacin or propranolol given instead of L-NAME. The effect of a single dose of methylene-blue, given before noradrenaline, was tested in control rats in varying doses between 2 x 10(-6) and 2 x 10(-4) M. In the highest concentration it made no difference whether insulin was given or not and there was a similar relaxing effect in diabetic and control arteries. In conclusion, the present study showed that insulin per se has a relaxing effect on renal arteries. There was a tendency to greater relaxation in diabetic than in control rats, an effect which was attenuated by in-vitro-pretreatment with L-NAME as well as with L-NAME and L-arginine in diabetic vessels, while relaxation was increased in control vessels. This may indicate that the effect of insulin may be mediated through nitric oxide in diabetic but not in control rats. The effects of insulin in control vessels were not modified in vitro by indomethacin, propranolol or methylene-blue.     

Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated with curcumin and/or insulin

This study evaluated the effects of curcumin and/or insulin on antioxidant enzyme activity in blood, liver, and kidney, as well as on lipid peroxidation and delta aminolevulinic dehydratase (δ-ALA-D) activity, and a histopathological analysis of streptozotocin-induced diabetic rats. The animals were divided into six groups (n = 6): control/saline (C); control/curcumin (CCur); diabetic/saline (D); diabetic/insulin (DIns); diabetic/curcumin (DCur); and diabetic/insulin/curcumin (DInsCur). After 30 days of treatment with curcumin and/or insulin, the animals were sacrificed and the liver, kidney, and serum were used for experimental determinations. Results of histopathological analysis showed that the treatment with insulin ameliorate renal and hepatic lesions from both DIns and DInsCur groups. TBARS levels were significantly increased in serum, liver, and kidney in D group and the administration of curcumin and insulin prevented this increase in DIns and DCur groups. The activities of catalase (CAT), superoxide dismutase, and δ-ALA-D presented a significant decrease in the liver and kidney D group when compared to C group (P < 0.05). The animals treated with curcumin and insulin presented an increase of CAT activity, revealing a positive interaction between both substances. The treatments with curcumin or insulin prevented oxidative stress in blood, through modulation of enzymatic antioxidant defenses. These findings contributed to the comprehension that antioxidants from medicinal plants could be used as adjuvant in the treatment of this endocrinopathy and not as single therapy.     

The effect of thyroid hormones on the membrane adenylate cyclase activity in sickle red blood cells in vitro

A comparative study of thyroid hormone responsive membrane adenylate cyclase activity has been carried out on normal (Hb-AA) and sickle cell (Hb-SS) subjects. Thyroid hormones (T3 and T4) and selected analogues (TRIAC and DLT) enhanced adenylate cyclase activity in Hb-AA membranes. The interaction of Hb-SS membranes with the hormones and analogues was not significant except for T3 which moderately stimulated Hb-SS membrane adenylate cyclase. We suggest that circulating irreversibly sickled cells, in view of their membrane phospholipid defect, probably contribute to the low response of membrane adenylate cyclase to effector stimulation.