Betaine supplementation to rats alleviates disturbances induced by high-fat diet: pleiotropic effects in model of type 2 diabetes.

Betaine is a biologically active compound exerting beneficial effects in the organism, however, the exact mechanisms underlying its action are not fully elucidated. The present study aimed to explore, whether betaine alleviates disorders induced by feeding rats a high-fat diet (HFD). Rats were divided into 3 groups: control, fed an HFD and fed an HFD and receiving betaine (2% water solution for 8 weeks). Betaine improved glucose tolerance, decreased blood levels of non-esterified fatty acids and prevented lipid accumulation in the skeletal muscle of rats on an HFD. Betaine reduced activities of blood alanine aminotransferase, blood levels of bilirubin and hepatic lipid content. Expression of fatty acid synthase in the liver and the skeletal muscle was decreased in response to feeding an HFD, and this effect was deepened by betaine in the muscle tissue. Hepatic and muscular expression of genes related to insulin signaling were unchanged in HFD-fed rats. Lipolysis stimulated by epinephrine (an adrenergic receptor agonist), forskolin (an activator of adenylate cyclase), dibutyryl-cAMP (an activator of protein kinase A) and DPCPX (an adenosine A1 receptor antagonist) was diminished in the adipocytes of rats fed an HFD, however, this effect was alleviated by betaine. Moreover, blood leptin levels in HFD-fed rats were elevated, whereas leptinemia have normalized by betaine supplementation. Betaine prevented the increase in expression of N-methyl D-aspartate receptors in the hippocampus and in the cerebral cortex. These results indicate that betaine positively affects the insulin-sensitive tissues: liver (hepatoprotective effects), skeletal muscle (reduced lipid accumulation) and adipose tissue (a rise in lipolysis), which is associated with improved insulin sensitivity. Betaine-induced prevention of hyperleptinemia indicates restoration of leptin action, and changes in the brain reveal neuroprotective properties. Our results show that betaine induces positive changes in HFD-fed rats, its action is pleiotropic and involves different tissues.

Resveratrol reduces excessive cholesterol accumulation in Goto-Kakizaki rat, a model with congenital type 2 diabetes.

Resveratrol (3, 5, 3'-trihydroxystilbene) is a naturally-occurring, biologically active compound having numerous beneficial effects in the organism, including anti-diabetic properties. Its anti-diabetic action have been relatively well established using various animal models, however, in Goto-Kakizaki (GK) rats is poorly explored. These animals are non-obese and have a congenital type 2 diabetes. In the present study, effects of resveratrol on cholesterol content, blood levels of some hormones (thyroxine, triiodothyronine, ghrelin and spexin), glucose and parameters indirectly related with renal function (creatinine, urea nitrogen, total protein and albumin) were explored in GK rats. GK and control rats were treated with resveratrol for 10 weeks at the dose of 20 mg/kg body weight. It was shown that cholesterol content was significantly increased in the blood, liver and the skeletal muscle of diabetic rats, compared with the control animals. However, the resveratrol therapy was associated with a markedly reduced tissue cholesterol content. Our study also demonstrated that blood levels of thyroxine (T4) were decreased, and triiodothyronine (T3) increased in GK rats. These alterations were, however, not significantly affected by resveratrol. GK rats had elevated blood glucose levels, but hyperglycemia was not ameliorated by resveratrol. It was also shown that blood creatinine levels were increased in diabetic rats. However, in animals subjected to the resveratrol therapy, the blood creatinine level was unchanged. Concentrations of ghrelin, spexin and other blood parameters indirectly related with the renal function were shown to be similar in GK and control rats. These results indicate that resveratrol beneficially influences cholesterol concentrations in tissues of diabetic rats; however, it is ineffective in the case of thyroid hormones and glucose. Moreover, it was shown that resveratrol did not induce any significant effects in non-diabetic animals.

The time-dependent effect of gluconasturtiin and phenethyl isothiocyanate on metabolic and antioxidative parameters in rats.

The effect of gluconasturtiin (GNST) and phenethyl isothiocyanate (PEITC) on some metabolic changes and antioxidative parameters in the rat was tested using different doses of PEITC and duration of GNST or PEITC ingestion. Their effect on antioxidative processes was previously observed, however, their influence on metabolic changes is still poorly characterized. In the performed experiment, the effect of GNST (0.5 mg/kg BW) and PEITC (0.1 mg/kg BW or 0.3 mg/kg BW) administered intragastrically after 4 h or 14 days to growing male rats was studied. PEITC at both doses after 4 h of its administration caused a considerable increase in liver cholesterol and triglyceride content with a concomitant drop in the amount of glycogen. Blood glucose, free fatty acids, phospholipids and total, free, esterified cholesterol as well as cholesterol in high-density lipoprotein were not altered. GNST, at its short-time ingestion, augmented significantly the concentration of triglycerides in blood serum. The compounds tested had no influence on metabolic changes after a longer period of action with the exception of glycogen values in liver, which were substantially augmented by PEITC at both doses. Our trial revealed a lack of GNST and PEITC influence on the content of liver sulphhydryl groups and on glutathione peroxidase and glutathione-S-transferase activities. The only distinct change in the content of malonodialdehyde was observed after short-time action of lower dose of PEITC. Our research showed that the short-term PEITC action constituted a significant factor interfering with liver metabolism. Although PEITC has been repeatedly advocated as very promising anticancer agent, in our experiment, the lower dose of PEITC was revealed as a pro-oxidative substance. These inconsistent properties seem to depend on its dose and time of action.

The influence of fasting on liver sulfhydryl groups, glutathione peroxidase and glutathione-S-transferase activities in the rat.

Sulfhydryl groups, glutathione peroxidase (GPx) and glutathione-S-transferase (GST) are important elements of the antioxidant defence in the organism. The efficacy of their antioxidant action is influenced by many factors. In this work, the effect of fasting on total, protein-bound and nonprotein sulfhydryl groups and on the activity of liver and serum GPx and GST in rats were determined. Male Wistar rats were divided into two groups: non-fasted and 18-hour fasted. In fasted animals liver content of nonprotein sulfhydryl groups (represented predominantly by reduced glutathione; GSH) was diminished by 22% in comparison to non-fasted group, whereas total and protein-bound -SH groups were unaffected. The activity of liver and serum GPx was unchanged in food deprived rats. In these animals the activity of GST in serum was reduced by 26%. Fasting had no significant effect on the activity of GST in the liver. Our results demonstrate that in rats deprived of food for 18 hours liver and serum GPx and GST are not involved in protection against action of reactive oxygen species formed during fasting. The observed drop in the content of liver nonprotein sulfhydryl groups without concomitant rise in the activity of GPx and GST indicates that this effect may be due to augmented degradation of GSH, its potentiated efflux from hepatocytes and formation of conjugates with intermediates arising as a result of reactive oxygen species action.

Alloxan in vivo does not only exert deleterious effects on pancreatic B cells.

The aim of the experiment was to investigate the mechanism of harmful alloxan action in vivo. 75 mg/kg b.w. of this diabetogenic agent were administered to fasting rats. Two minutes later the animals were decapitated. It was observed that alloxan caused a distinct rise in blood insulin and glucose levels with a concomitant drop of free fatty acids. The amount of sulfhydryl groups in the liver of alloxan-treated rats was decreased and glutathione peroxidase activity was substantially higher. These results indicate that some changes observed in alloxan-induced diabetes can not only be the consequence of B cells damage by alloxan but may also be the result of its direct influence on other tissues. It was also observed that glucose given 20 min before alloxan injection only partially protected against the deleterious effects of alloxan.