title: Estimation of ellagic acid and/or repaglinide effects on insulin signaling, oxidative stress, and inflammatory mediators of liver, pancreas, adipose tissue, and brain in insulin resistant/type 2 diabetic rats.
abstract: Even though ellagic acid has previously been valued in many models of cancer, so far its full mechanistic effect as a natural antiapoptotic agent in the prevention of type 2 diabetes complications has not been completely elucidated, which was the goal of this study. We fed albino rats a high-fat fructose diet (HFFD) for 2 months to induce insulin resistance/type 2 diabetes and then treated the rats with ellagic acid (10 mg/kg body weight, orally) and/or repaglinide (0.5 mg/kg body weight, orally) for 2 weeks. At the serum level, ellagic acid challenged the consequences of HFFD, significantly improving the glucose/insulin balance, liver enzymes, lipid profile, inflammatory cytokines, redox level, adipokines, ammonia, and manganese. At the tissue level (liver, pancreas, adipose tissue, and brain), ellagic acid significantly enhanced insulin signaling, autophosphorylation, adiponectin receptors, glucose transporters, inflammatory mediators, and apoptotic markers. Remarkably, combined treatment with both ellagic acid and repaglinide had a more pronounced effect than treatment with either alone. These outcomes give new insight into the promising molecular mechanisms by which ellagic acid modulates numerous factors induced in the progression of diabetes.
authors.affiliation: Department of Pharmacology, Medical Division, National Research Centre, 33 EL Bohouth St., Dokki, Giza 12622, Egypt.|Department of Pharmacology, Medical Division, National Research Centre, 33 EL Bohouth St., Dokki, Giza 12622, Egypt.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Amin
authors.affiliation: Department of Pharmacology, Medical Division, National Research Centre, 33 EL Bohouth St., Dokki, Giza 12622, Egypt.|Department of Pharmacology, Medical Division, National Research Centre, 33 EL Bohouth St., Dokki, Giza 12622, Egypt.
authors.forename: Mahmoud S
authors.initials: MS
authors.lastname: Arbid
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002219:Carbamates / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004359:Drug Therapy, Combination; D004610:Ellagic Acid / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010880:Piperidines / Q000627:therapeutic use*; D017208:Rats, Wistar
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015415:Biomarkers; D002219:Carbamates; D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D010880:Piperidines; D004610:Ellagic Acid; C072379:repaglinide
keywords: acide ellagique; diabète de type 2; ellagic acid; insulin resistance; insulinorésistance; rats; repaglinide; répaglinide; type 2 diabetic rats