Effect of topiramate on serum biomarkers.

<p>The panels illustrate the effect of topiramate (40 & 100 mg/kg, p.o; TPM₄₀, TPM₁₀₀) on serum (A) triglycerides (TGs, [mg/dl]), (B) total cholesterol(TC, [mg/dl]), (C) free fatty acids (FFAs, mmol/l]), (D)ALT (IU/L), (E) tumor necrosis alpha (TNF-α, [pg/ml]) and (F) adiponectin [ng/ml] of obese/insulin resistant rats fed high fat and high fructose diet [HFFD] for 10 weeks (mean of 10 animals ± S.D.). Treatments were administered once daily for 2 weeks. As compared with normal control (^*), HFFD (<b>^†</b>) and HFFD+TPM40 ^(<b>‡</b>) groups (one-way ANOVA followed by Tukey–Kramer Test), <i>P</i><0.05.</p

Effect of topiramate on hepatic biomarkers.

<p>The panels illustrate the effect of topiramate (40 & 100 mg/kg, p.o; TPM₄₀, TPM₁₀₀) on hepatic (A, B) insulin receptor isoforms (high affinity, [HAIR, fmol/mg protein] and low affinity [LAIR, pmol/mg protein] insulin receptor), (C, D) adiponectin receptors (Adipo-R1, Adipo-R2 [ng/mg protein]), (E) protein tyrosine kinase (PTK [U/mg protein]), and (F) glucose transporter-2 (GLUT2 [mg/mg protein]) of obese/insulin resistant rats fed high fat and high fructose diet [HFFD] for 10 weeks (mean of 10 animals ± S.D.). Treatments were administered once daily for 2 weeks. As compared with normal control (^*), HFFD (<b>^†</b>) and HFFD+TPM40 ^(‡) groups (one-way ANOVA followed by Tukey–Kramer Test), <i>P</i><0.05.</p

Effect of topiramate on the indicators of glucose homeostasis of obese/insulin resistant rats.

<p>Effect of topiramate (40, 100 mg/kg; TPM₄₀, TPM₁₀₀) on serum levels of glucose, insulin, and fructosamine, HOMA-index and area under the curve of the GTT of obese/insulin resistant rats fed high fat and high fructose diet [HFFD] for 10 weeks. Values are means (± S.D.) of 10 animals. Treatments were administered once daily for 2 weeks. As compared with normal control (^*), HFFD (<b>^†</b>) and HFFD+TPM₄₀<b>(^‡)</b> groups (one-way ANOVA followed by Tukey–Kramer Test), <i>P</i><0.05.</p

Effect of topiramate on serum and tissue biomarkers of normal control rat.

<p>Effect of 14 days administration of topiramate (40, 100 mg/kg) to normal control rats fed normal diet. The following markers were assessed: serum levels of glucose, insulin, and fructosamine, HOMA-index and area under the curve (AUC); serum triglycerides (TGs), total cholesterol (TC), free fatty acids (FFAs), ALT (IU/L), tumor necrosis alpha (TNF-α) and adiponectin; body weight (BW) and liver weight (LW)/−, visceral fat weight (VFW)/− and epididymal fat weight (EFW)/−BW ratio. Values are means (± S.D.) of 10 animals. Treatments were administered once daily for 2 weeks. Statistical analysis between groups was carried out using one-way ANOVA followed by Tukey-Kramer Test, <i>P</i><0.05.</p

Correlation coefficient (<i>r</i>) between HOMA-I and serum adiponectin with hepatic GLUT2, adiponectin receptors (Adipo- R1, R2), insulin receptor isoforms (LAIR, HAIR), and tyrosine kinase.

<p>Correlation was carried out in untreated and treated hyperglycemic animals.</p

The glucose tolerance test (GTT).

<p>The curve depicts the changes in serum glucose response in normal control, non-treated obese/insulin-resistant rats (HFFD), and treated ones by either dose of topiramate (40 & 100 mg/kg;HFFD+TPM40, HFFD+TPM₁₀₀), after 0, 30, 60, 90, and 120 min following administration of glucose (2 g/kg, ip). Values are means (± S.D) of 10 animals; as compared with normal control (^*), and HFFD (<b>^†</b>) groups (one-way ANOVA followed by Tukey–Kramer Test), <i>P</i><0.05.</p

Effect of topiramate on body-, liver- and fat weights of obese/insulin resistant rats.

<p>Effect of topiramate (40, 100 mg/kg; TPM₄₀, TPM₁₀₀) on body weight (BW) and liver weight (LW)/−, visceral fat weight (VFW)/− and epididymal fat weight (EFW)/−BW ratio of obese/insulin resistant rats fed high fat and high fructose diet [HFFD] for 10 weeks. Values are means (± S.D.) of 10 animals. Treatments were administered once daily for 2 weeks. As compared with normal control (<b>^*</b>), and HFFD (<b>^†</b>) groups (one-way ANOVA followed by Tukey-Kramer Test), <i>P</i><0.05.</p

Effect of diabetes (DV) and different oral drug regimens on the serum lipid profile.

<p>Effect of diabetes (DV) and different oral drug regimens, viz., phytol (DP_h, 250 mg/kg); pioglitazone (DP₅, 5 mg/kg); pioglitazone (DP₁₀, 10 mg/kg); phytol and pioglitazone (DP_hP₅); on serum levels of triglycerides, total cholesterol, LDL-C, HDL-C, ALT and TC/HDL ratio (mean of 7 animals ± S.D). As compared with non-diabetic [ND] (*) and diabetic [DV] (#) groups using one way ANOVA followed by Tukey post hoc test, <i>P</i><0.05. (^Ο) Significant interaction when P_h and P₅ were combined using Factorial Design.</p

ICM scores of phytanic acid, retinoic acid, pioglitazone, and rosiglitazone docked in 1FM6 crystal structure binding site and hydrogen bonds formed with amino acid residues.

<p>ICM scores of phytanic acid, retinoic acid, pioglitazone, and rosiglitazone docked in 1FM6 crystal structure binding site and hydrogen bonds formed with amino acid residues.</p

Effect of diabetes (DV) and different oral drug regimens on glucose homeostasis indicators.

<p>Effect of diabetes (DV) and different oral drug regimens, viz., phytol (DP_h, 250 mg/kg); pioglitazone (DP₅, 5 mg/kg); pioglitazone (DP₁₀, 10 mg/kg); phytol and pioglitazone (DP_hP₅); on serum levels of glucose, insulin, fructosamine, TNF-α, adiponectin and insulin resistance (HOMA-ratio) (mean of 7 animals ± S.D). As compared with non-diabetic [ND] (*) and diabetic [DV] (#) groups using one way ANOVA followed by Tukey post hoc test, <i>P</i><0.05. (^Ο) Significant interaction when P_h and P₅ were combined using Factorial Design.</p