title: Astaxanthin prevents loss of insulin signaling and improves glucose metabolism in liver of insulin resistant mice.
abstract: This study investigates the effects of astaxanthin (ASX) on insulin signaling and glucose metabolism in the liver of mice fed a high fat and high fructose diet (HFFD). Adult male Mus musculus mice of body mass 25-30 g were fed either normal chow or the HFFD. After 15 days, mice in each group were subdivided among 2 smaller groups and treated with ASX (2 mg·(kg body mass)⁻¹) in olive oil for 45 days. At the end of 60 days, HFFD-fed mice displayed insulin resistance while ASX-treated HFFD animals showed marked improvement in insulin sensitivity parameters. ASX treatment normalized the activities of hexokinase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase, and increased glycogen reserves in the liver. Liver tissue from ASX-treated HFFD-fed animals showed increased tyrosine phosphorylation and decreased serine phosphorylation of insulin receptor substrates (IRS)-1 and -2. ASX increased IRS 1/2 and phosphatidylinositol 3-kinase (PI3K) association and serine phosphorylation of Akt. In addition, ASX decreased HFFD-induced serine kinases (c-jun N-terminal kinase-1 and extracellular signal-regulated kinase-1). The results suggest that ASX treatment promotes the IRS-PI3K-Akt pathway of insulin signaling by decreasing serine phosphorylation of IRS proteins, and improves glucose metabolism by modulating metabolic enzymes.
authors.affiliation: Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar 608 002, Tamil Nadu, India.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Bhuvaneswari
authors.forename: Carani Venkatraman
authors.initials: CV
authors.lastname: Anuradha
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D019587:Dietary Supplements; D006943:Hyperglycemia / Q000178:diet therapy* / Q000209:etiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D055504:Insulin Receptor Substrate Proteins / Q000819:agonists* / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D058539:Phosphatidylinositol 3-Kinase / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000378:metabolism; D011897:Random Allocation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism; D024341:Xanthophylls / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D007004:Hypoglycemic Agents; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse; D008112:Liver Glycogen; D024341:Xanthophylls; D014443:Tyrosine; D012694:Serine; C005948:astaxanthine; D058539:Phosphatidylinositol 3-Kinase; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt