Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat.

Troxerutin is a trihydroxyethylated derivative of the flavonoid, rutin. It has been reported to possess the hepatoprotective, nephroprotective, antioxidant, anti-inflammatory, and antihyperlipidemic activities. Troxerutin treatment reduced the blood glucose and glycosylated hemoglobin levels in high-cholesterol-induced insulin-resistant mice and in type-2 diabetic patients. However, the mechanism by which it exhibits antidiabetic property was unknown. Therefore, the present study was designed to evaluate the effect of troxerutin on insulin signaling molecules in gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic rats. Wistar male albino rats were selected and divided into five groups. Group I: Control. Group II: High fat and sucrose-induced type-2 diabetic rats. Group III: Type-2 diabetic rats treated with troxerutin (150 mg/kg body weight/day orally). Group IV: Type-2 diabetic rats treated with metformin (50 mg/kg body weight/day orally). Group V: Normal rats treated with troxerutin (150 mg/kg body weight/day orally). After 30 days of treatment, fasting blood glucose, oral glucose tolerance, serum lipid profile, and the levels of insulin signaling molecules, glycogen, glucose uptake, and oxidation in gastrocnemius muscle were assessed. Diabetic rats showed impairment in insulin signaling molecules (IR, p-IRS-1(Tyr632), p-Akt(Ser473), ß-arrestin-2, c-Src, p-AS160(Thr642), and GLUT4 proteins), glycogen concentration, glucose uptake, and oxidation. Oral administration of troxerutin showed near normal levels of blood glucose, serum insulin, lipid profile, and insulin signaling molecules as well as GLUT4 proteins in type-2 diabetic rats. It is concluded from the present study that troxerutin may play a significant role in the management of type-2 diabetes mellitus, by improving the insulin signaling molecules and glucose utilization in the skeletal muscle.

Estradiol favors glucose oxidation in gastrocnemius muscle through modulation of insulin signaling molecules in adult female rats.

INTRODUCTION: Estrogens are steroid compounds that are synthesized in ovary, testis, adrenal cortex and other tissues. Several surveys have shown the potential relationship between estradiol and glucose homeostasis in physiological and pathological states such as the menstrual cycle, gestation, gestational diabetes mellitus and polycystic ovarian syndrome (PCOS). All these states are characterized by variability in estradiol level and some degree of insulin resistance. Skeletal muscle plays a crucial role in maintaining systemic glucose metabolism through activation of assorted signaling molecules. OBJECTIVES: The present study is to evaluate the aftermath of ovariectomy and estradiol replacement on few insulin signaling molecules and GLUT4 protein expression and glucose oxidation in gastrocnemius muscle of adult albino rat. DESIGN: In the present study, Wistar strain albino rats were selected and divided into three groups. Group I: Control (sham-operated). Group II: Ovariectomized and Group III: Estradiol was replaced 7 days after ovariectomy at a dose of 6 µg/kg boxpression of insulin signaling molecules (western blot) and glucose oxidation were assessed. RESULTS: Ovariectomy significantly depleted the expression of insulin signaling molecules and glucose oxidation whereas estradiol replacement improved them. Thus, estradiol helps in maintaining glucose level in ovariectomized rats. Results of this study suggest that estradiol improves the expression of insulin signaling molecules in skeletal muscle and thereby it prevents the onset of insulin resistance as a result of estradiol deficiency.

Effect of homeopathic preparations of Syzygium jambolanum and Cephalandra indica on gastrocnemius muscle of high fat and high fructose-induced type-2 diabetic rats.

BACKGROUND: Homeopathy is a holistic method of treatment that uses microdoses of natural substances originating from plants, minerals, or animal parts. Syzygium jambolanum and Cephalandra indica are used in homeopathy for treatment of type-2 diabetes. However, the molecular mechanisms responsible for such effects are not known. METHODS: Homeopathic preparations of S. jambolanum and C. indica in mother tincture, 6c and 30c were used to examine the molecular mechanism of antidiabetic effects in the skeletal muscle of rats with high fat and fructose-induced type-2 diabetes mellitus. After 30 days treatment, fasting blood glucose, serum insulin and insulin signaling molecules in the skeletal muscle (gastrocnemius) were measured. RESULTS: Diabetic rats showed a significant decrease in serum insulin and lipid profile as well as low levels of insulin receptor (IR), v-akt murine thymoma viral oncogene homolog (Akt), p-Akt(ser473) and glucose transporter-4 (GLUT4) protein expression (p < 0.05) with a significant increase in fasting blood glucose level (p < 0.05) compared to the control group. Treatment with homeopathic remedies significantly increased the serum insulin and expression of these proteins (p < 0.05) with a significant decrease in fasting blood glucose (p < 0.05) compared to diabetic rats. CONCLUSIONS: In the present study homeopathic preparations of S. jambolanum and C. indica, including ultramolecular dilutions exhibit antidiabetic effects, improving insulin action through activation of insulin signaling molecules in skeletal muscle of type-2 diabetic rats.