V. Thirunavukkarasu

Influence of alpha-lipoic acid on lipid peroxidation and antioxidant defence system in blood of insulin-resistant rats.

Background:  High fructose feeding induces insulin resistance and hyperinsulinaemia in rats. A role for oxidative stress in the occurrence of insulin resistance has been suggested by several workers.

Taurine modifies insulin signaling enzymes in the fructose-fed insulin resistant rats.

OBJECTIVES High fructose feeding induces insulin resistance and hyperinsulinemia in rats. The present study was proposed to elucidate the derangements in the insulin signaling pathway in high fructose-fed rats and whether taurine, a sulphur-containing amino acid could improve insulin action by modulating the signal transduction pathway. METHODS Male Wistar rats of body weight 170-190 g were divided into 4 groups of 6 rats each. Control rats received control diet and water ad libitum. Fructose fed animals received high fructose diet (> 60% of total calories) and water ad libitum. Fructose + taurine rats received fructose diet and 2% taurine solution ad libitum. Control + taurine rats received control diet and 2% taurine solution ad libitum. After the experimental period of 30 days, the effects of taurine on certain parameters on glucose metabolism were determined. The activities of protein tyrosine kinase (PTK) and protein tyrosine phosphatase (PTP) were assayed in liver. RESULTS The activities of the glycolytic enzymes were significantly lower while the activities of the gluconeogenic enzymes were higher in untreated fructose-fed rats as compared to control animals. Depletion of liver glycogen was observed in fructose-fed rats. Fructose-fed rats showed alterations in the activities of insulin signaling enzymes PTK and PTP. Taurine administration improved insulin sensitivity and controlled hyperglycemia and hyperinsulinemia in fructose-fed rats. Taurine treatment also restored the glucose metabolizing enzyme activities in fructose-fed rats. CONCLUSIONS Taurine supplementation might have a beneficial effect in overcoming insulin resistance and its associated abnormalities by modifying the post-receptor events of insulin action.

Effect of α-Lipoic Acid on Lipid Profile in Rats Fed a High-Fructose Diet

This study investigated the effect of administration of α-lipoic acid (LA) on lipid metabolism in high fructose–fed insulin-resistant rats. High-fructose feeding (60 g/100 g diet) to normal rats resulted in a significant increase in the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs), and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl–coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated. Treatment with LA (35 mg/kg body weight intraperitoneal) reduced the effects of fructose. The rats showed near-normal levels of lipid components on plasma and tissues. Activities of key enzymes of lipid metabolism were also restored to normal values. Cholesterol distribution in the plasma lipoproteins was normalized, resulting in a favorable lipid profile. This study demonstrates that LA can alter lipid metabolism in fructose-fed insulin-resistant rats and may have implications in the treatment of insulin resistance.

Cardiac lipids and antioxidant status in high fructose rats and the effect of α-lipoic acid

Abstract Background and Aims: The development of insulin resistance has been shown to be an early step in the development of cardiovascular diseases in diabetic patients. Oxidative stress may be important in the development of coronary artery disease. Fructose loaded rats, which show the characteristic features of insulin resistance, also display an imbalance between the peroxidation process and the antioxidant system. Alpha-lipoic acid (LA) — a co-enzyme — is known for its potent antioxidant effects. The present study examined whether LA mitigates fructose-induced oxidative stress in heart tissue. Methods and Results: Male Wistar rats with a body weight of 150–170g were divided into 4 groups of 6 rats each. Control rats received a control diet containing starch and water ad libitum . Fructose rats received a fructose-enriched diet (>60% of total calories). Fructose + LA rats received a fructose diet and α -lipoic acid (35mg/kg b.w i.p.). Control + LA rats received control diet and α -lipoic acid. After the 20-day treatment period, we assessed the insulin sensitivity index in terms of HOMA. The levels of lipid peroxidation markers and the enzymatic and non-enzymatic antioxidant status in the heart tissue were measured. Plasma and heart tissue lipids were also analysed. Fructose rats showed decreased insulin sensitivity as reflected by high values of HOMA, increased peroxidation, impaired antioxidant status and lipid abnormalities in the cardiac tissue. These abnormalities were attenuated and the antioxidant levels were enhanced by LA. The reduction in HOMA values suggests LA improves insulin sensitivity. Conclusions: Improvement of insulin sensitivity and enhancement of cardiac antioxidant status suggest that LA may be useful as a cardioprotective agent in insulin-resistant states.

Fructose Diet-Induced Skin Collagen Abnormalities Are Prevented by Lipoic Acid

Nonenzymatic glycation of proteins, leading to chemical modification and cross-linking are of importance in the pathology of diabetic complications.We studied the effect of α-lipoic acid (LA) on the content and characteristics of the protein collagen from skin of high-fructose fed rats. The rats were divided into 4 groups of 6 each. Two groups of rats were fed with a high fructose diet (60 g/100 g diet) and administered either LA (35 mg/kg b.w., i.p) (FRU+LA) or 0.2 ml vehicle (saline) (FRU) for 45 days. The other 2 groups were fed with control diet containing starch (60 g/100 g diet) and administered either saline (CON) or lipoic acid (CON+LA). The rats were maintained for 45 days and then sacrificed. Plasma glucose, insulin, fructosamine, protein glycation, and blood glycated hemoglobin (HbA1C) were measured. Collagen was isolated from skin and the physicochemical properties of collagen were studied. Fructose administration caused accumulation of collagen in skin. Extensive cross-linking was evidenced by enhanced glycation and AGE-linked fluorescence. Increased peroxidation and changes in physicochemical properties such as shrinkage temperature, aldehyde content, solubililty pattern, susceptibility to denaturing agents were observed in fructose-fed rats. SDS gel pattern of collagen from these rats showed elevated β component of type I collagen. These changes were alleviated by the simultaneous administration of LA. Administration of LA to fructose-fed rats had a positive influence on both quantitative and qualitative properties of collagen. The results suggest a mechanism for the ability of LA to delay diabetic complications.

Influence of 6-week exercise training on erythrocyte and liver antioxidant defense in hyperinsulinemic rats

High dosage of fructose in rats causes insulin resistance and hyperinsulinemia. This study investigates the effect of physical exercise on oxidant-antioxidant balance in rats fed a high fructose diet, which show characteristic features of insulin resistance. Products of lipid peroxidation and the activity of enzymic antioxidants namely superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase, in red blood cells (RBCs) and liver were assayed. Levels of non-enzymic antioxidants alpha-tocopherol and ascorbic acid and of protein and non-protein thiols were also determined. The levels of lipid peroxides, diene conjugates, lipofuscin and hydroperoxides were significantly higher in the liver of fructose-fed rats. The RBCs showed significantly higher susceptibility to H(2)O(2)-induced stress compared to control rats. Inadequate antioxidant system was noted in high fructose-fed rats. Physical training to these rats reversed the adverse effects, which could be important in alleviating the pathological consequences of insulin resistance.

Lipoic acid prevents collagen abnormalities in tail tendon of high‐fructose‐fed rats

Background:  Non‐enzymatic glycation of proteins, leading to chemical modification and cross‐linking are of importance in the pathology of diabetic complications. We studied the effect of α‐lipoic acid (LA) on the glycation and cross‐linking of collagen from tail tendon of high‐fructose‐fed rats.