Topiramate-Induced Modulation of Hepatic Molecular Mechanisms: An Aspect for Its Anti-Insulin Resistant Effect

Topiramate is an antiepileptic drug known to ameliorate insulin resistance besides reducing body weight. Albeit liver plays a fundamental role in regulation of overall insulin resistance, yet the effect of topiramate on this organ is controversial and is not fully investigated. The current work aimed to study the potential hepatic molecular mechanistic cassette of the anti-insulin resistance effect of topiramate. To this end, male Wistar rats were fed high fat/high fructose diet (HFFD) for 10 weeks to induce obese, insulin resistant, hyperglycemic animals, but with no overt diabetes. Two HFFD-groups received oral topiramate, 40 or 100 mg/kg, for two weeks. Topiramate, on the hepatic molecular level, has opposed the high fat/high fructose diet effect, where it significantly increased adiponectin receptors, GLUT2, and tyrosine kinase activity, while decreased insulin receptor isoforms. Besides, it improved the altered glucose homeostasis and lipid profile, lowered the ALT level, caused subtle, yet significant decrease in TNF-α, and boosted adiponectin in a dose dependent manner. Moreover, topiramate decreased liver weight/, visceral fat weight/, and epididymal fat weight/body weight ratios. The study proved that insulin-resistance has an effect on hepatic molecular level and that the topiramate-mediated insulin sensitivity is ensued partly by modulation of hepatic insulin receptor isoforms, activation of tyrosine kinase, induction of GLUT2 and elevation of adiponectin receptors, as well as their ligand, adiponectin, besides its known improving effect on glucose tolerance and lipid homeostasis

Adiponectin Single Nucleotide Polymorphism (+276G/T) and Its Possible Relation to Adiponectin Level in Egyptian Patients with Coronary Artery Disease

Increasing interest has been directed toward the role of the adiponectin gene polymorphism in the human genome and its implication in the pathogenesis of coronary artery disease. The present study was investigating the association between the single nucleotide polymorphism +276 G/T of the adiponectin gene with serum adiponectin level in patients with coronary artery disease (CAD). In this study 100 healthy controls and 100 Egyptian patients with coronary artery disease of both genders presented to the Cardiology Department of Suez Canal University Hospital were investigated. All subjects were genotyped for +276 G/T polymorphism of adiponectin gene. Lipid profile, fasting blood glucose were measured. Adiponectin and high sensitivity C-reactive protein levels were determined by ELISA technique. Polymerase chain reaction based on restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes of the studied population. The lowest serum adiponectin value was observed in patients with CAD compared with control group. The T allele of SNP +276 G/T in the adiponectin gene was found to be associated with CAD (odd ratio 2.23; 95% CI: 1.44-3.45; P= 0.001). The significantassociation of the T allele (GT+TT) of this SNP with lower adiponectin level  and higher hsCRP levels was confirmed in the study (p= 0.003 and 0.006 respectively). Our results concluded that, +276 G/T SNP in the adiponectin gene is associated with CAD. Furthermore, carriers of the at-risk T allele had lower serum adiponectin level and higher serum hsCRP, causing in turn an increased risk to develop CAD.Key Words: Adiponectin gene; polymorphism; Coronary artery disease; PCR-RFL