title: Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases.
abstract: Emerging evidence suggests that high fructose consumption may be a potentially important factor responsible for the rising incidence of insulin resistance and diabetes worldwide. The present study investigated the preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high fructose fed male Wistar rats at the molecular level. Fructose feeding for 10 weeks caused oxidative stress, inflammation and insulin resistance. Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats. It also attenuated hyperinsulinemia, glucose intolerance and HOMA-IR level. Curcumin administration lowered tumor necrosis factor alpha (TNF-α), C reactive protein (CRP) levels and downregulated the protein expression of cyclo-oxygenase 2 (COX-2), protein kinase theta (PKCθ). In addition, inhibitor κB alpha (IκBα) degradation was prevented by curcumin supplementation. Treatment with curcumin inhibited the rise of malondialdehyde (MDA), total oxidant status (TOS) and suppressed the protein expression of extracellular kinase ½ (ERK ½), p38 in the skeletal muscle of fructose fed rats. Further, it enhanced Glutathione Peroxidase (GPx) activity in the muscle of fructose fed rats. At the molecular level, curcumin inhibited the activation of stress sensitive kinases and inflammatory cascades. Our findings conclude that curcumin attenuated glucose intolerance and insulin resistance through its antioxidant and anti-inflammatory effects. Thus, we suggest the use of curcumin as a therapeutic adjuvant in the management of diabetes, obesity and their associated complications.
authors.affiliation: Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605 006, India.
authors.forename: Nachimuthu
authors.initials: N
authors.lastname: Maithilikarpagaselvi
authors.affiliation: Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605 006, India. Electronic address: sridhar_biochem@yahoo.co.in.
authors.forename: Magadi Gopalakrishna
authors.initials: MG
authors.lastname: Sridhar
authors.affiliation: Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605 006, India.
authors.forename: Rathinam Palamalai
authors.initials: RP
authors.lastname: Swaminathan
authors.affiliation: Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry 605 006, India.
authors.forename: Bobby
authors.initials: B
authors.lastname: Zachariah
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D018149:Glucose Intolerance / Q000517:prevention & control; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000188:drug therapy / Q000517:prevention & control*; D007333:Insulin Resistance; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005632:Fructose; D017346:Protein Serine-Threonine Kinases; D003474:Curcumin
keywords: Curcumin; Fructose rich diet; Insulin sensitivity; Low grade inflammation; Metabolic derangement; Oxidative stress