The influence of glimepiride on the binding kinetics of insulin with its skeletal muscle and liver receptors in rats with short term and prolonged hyperglycemia induced by streptozotocin.

BACKGROUND: The aim of the study was to determine the influence of glimepiride on the binding kinetics of insulin with its skeletal muscle receptor in rats with transient and prolonged hyperglycemia induced by streptozotocin. MATERIAL/METHODS: The studies were performed on healthy male Wistar rats with a body mass of 220+/-30 g, fed with LSM-type standard chow, and given water ad libitum. Transient or prolonged hyperglycemia was induced by intraperitoneal administration of streptozotocin. Blood samples were taken from the right heart ventricle to heparinized test tubes and centrifuged for 10 minutes at 700 i. g. Plasma was collected and the glucose level was determined. From each animal 1 g of skeletal muscle and 1 g of liver were collected as well, placed in liquid nitrogen and stored until determination of the affinity and number of receptors. RESULTS: We found an increase in affinity and binding capacity of high- and low-affinity receptors in rats with both transient and prolonged streptozotocin-induced hyperglycemia. The affinity and binding capacity of receptors increased under the influence of glimepiride in transient hyperglycemia caused by streptozotocin administration. CONCLUSIONS: The affinity and binding capacity of receptors increased under the influence of glimepiride in the course of transient hyperglycemia. The lack of changes in the specific insulin binding and binding capacity of receptors of both low and high affinity in the group of animals with prolonged hyperglycemia requires explanation.

The influence of glimepiride on the oxidative state of rats with streptozotocin-induced hyperglycemia.

BACKGROUND: The aim of this work was to determine whether glimepiride, a derivate of sulphonylurea of the hypoglycemic effect, influences the level of prooxidative factors and antioxidative enzymes activity in the course of experimental streptozotocin hyperglycemia in rats. MATERIAL/METHODS: The studies were performed on healthy male Wistar rats of body weight 200+/-30 g, fed with the standard laboratory diet and given water ad libitum. Animals were divided into 3 groups, each consisting of 8 rats. Group I--control animals, Group II--animals in which experimental hyperglycemia was induced by intraperitoneal administration of streptozotocin (65 mg/kg body mass), Group III--animals which were given glimepiride orally for seven weeks (200 mg/kg of body mass), starting 24 hours after streptozotocin administration. Using Ohkawa method, malondialdehyde level was determined in plasma for all groups. Concentration of hydrogen peroxide was determined using method developed by Frew and co-workers, superoxide dismutase activity using the Misra and Fridovich method and activity of glutathione peroxidase by means of Ransel kit [Randox, Great Britain]. The decrease of glucose level in serum of rats under the influence of streptozotocin and glimepiride was observed when compared with the group given placebo. RESULTS: Glimepiride administration caused a decrease of peroxides and malondialdehyde levels and increase in activity of superoxide dismutase and glutathione peroxidase in rats, after streptozotocin had been administered. CONCLUSIONS: The results suggest that glimepiride may effectively inhibit the development of the oxidative stress in diabetes.

The effect of brief food withdrawal on the level of free radicals and other parameters of oxidative status in the liver.

BACKGROUND: The aim of our study was to determine the effect of brief starvation on the level of free radicals and other parameters of oxidative status in the liver. MATERIAL/METHODS: The Wistar male rats used for the experiment were divided into two groups: Group I had free access to water and standard chow, while Group II was subjected to a 36-hour fast. The activity of antioxidant enzymes--catalase (CAT), glutathione peroxidase (GSH-Px) and Cu, Zn-superoxide dysmutase (CuZn-SOD)--was measured in the livers of both control and fasting animals. The hepatic level of free radicals and the concentration of malonyldialdehyde (MDA) were also determined in both groups of animals. RESULTS: Starvation resulted in decreased activity of CAT and CuZn-SOD, while the GSH-Px activity remained unchanged. Food deprivation also increased the level of free radicals. However, this rise was not paralleled by enhanced hepatic lipid peroxidation, measured as a change in MDA content. CONCLUSIONS: Since brief starvation causes an increase in the level of free radicals in the liver, it appears to effectively impair the tissue defence system, in part through the decreased activity of antioxidant enzymes, CAT and CuZn-SOD.