title: Featured Article: Oxidative stress status and liver tissue defenses in diabetic rats during intensive subcutaneous insulin therapy.
abstract: Long-term insulin delivery can reduce blood glucose variability in diabetic patients. In this study, its impact on oxidative stress status, inflammation, and liver injury was investigated. Diabetes was induced in Wistar rats with a single dose of streptozotocin (100 mg/kg). Untreated rats and rats administered Insuplant® (2 UI/200 g/day) through a subcutaneous osmotic pump for one or four weeks were compared with non-diabetic controls. Body weight, fructosamine level, total cholesterol, Insulin Growth Factor-1 (IGF-1) level, lipid peroxidation, and total antioxidant capacity were measured. Hepatic injury was determined through the measurement of glycogen content, reactive oxygen species (ROS) production, and macrophage infiltration. Liver oxidative stress status was evaluated through the measurement of superoxide dismutase (SOD), catalase (CAT), and nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) expression, and p38 mitogen-activated protein kinase (p38MAPK) activation. Induction of diabetes led to increased plasma oxidative stress and inflammation. Moreover, ROS production and macrophage infiltration increased in addition to SOD, CAT, and NADPH oxidase expression. Intensive insulin therapy improved metabolic control in diabetic animals as seen by a restoration of hepatic glycogen, plasma IGF-1 levels, and a decrease in plasma oxidative stress. However, insulin treatment did not result in a decrease in acute inflammation in diabetic rats as seen by continued ROS production and macrophage infiltration in the liver, and a decrease of p38MAPK activation. These results suggest that the onset of diabetes induces liver oxidative stress and inflammation, and that subcutaneous insulin administration cannot completely reverse these changes. Targeting oxidative stress and/or inflammation in diabetic patients could be an interesting strategy to improve therapeutic options.
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, 67200 Strasbourg, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dal
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, 67200 Strasbourg, France Structure d'Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, (HUS), 67000 Strasbourg, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jeandidier
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, 67200 Strasbourg, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Seyfritz
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, 67200 Strasbourg, France.
authors.forename: William
authors.initials: W
authors.lastname: Bietiger
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, 67200 Strasbourg, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Péronet
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, 67200 Strasbourg, France Structure d'Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, (HUS), 67000 Strasbourg, France.
authors.forename: François
authors.initials: F
authors.lastname: Moreau
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, 67200 Strasbourg, France Structure d'Endocrinologie, Diabète-Nutrition et Addictologie, Pôle NUDE, Hôpitaux Universitaires de Strasbourg, (HUS), 67000 Strasbourg, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Pinget
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, 67200 Strasbourg, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Maillard
authors.affiliation: UMR DIATHEC, EA 7294, Centre Européen d'Etude du Diabète, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, 67200 Strasbourg, France s.sigrist@ceed-diabete.org.
authors.forename: Séverine
authors.initials: S
authors.lastname: Sigrist
mesh_terms: D000818:Animals; D048909:Diabetes Complications; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology*; D006505:Hepatitis / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage*; D008264:Macrophages / Q000276:immunology; D008297:Male; D018384:Oxidative Stress; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Insulin therapy; diabetes; liver; oxidative stress