title: Maintenance of redox state and pancreatic beta-cell function: role of leptin and adiponectin.
abstract: Whereas oxidative stress is linked to cellular damage, reactive oxygen species (ROS) are also believed to be involved in the propagation of signaling pathways. Studies on the role of ROS in pancreatic beta-cell physiology, in contrast to pathophysiology, have not yet been reported. In this study we investigate the importance of maintaining cellular redox state on pancreatic beta-cell function and viability, and the effects of leptin and adiponectin on this balance. Experiments were conducted on RINm and MIN6 pancreatic beta-cells. Leptin (1-100 ng/ml) and adiponectin (1-100 nM) increased ROS accumulation, as was determined by DCFDA fluorescence. Using specific inhibitors, we found that the increase in ROS levels was mediated by NADPH oxidase (Nox), but not by AMP kinase (AMPK) or phosphatidyl inositol 3 kinase (PI3K). Leptin and adiponectin increased beta-cell number as detected by the XTT method, but did not affect apoptosis, indicating that the increased cell number results from increased proliferation. The adipokines-induced increase in viability is ROS dependent as this effect was abolished by N-acetyl-L-cysteine (NAC) or PEG-catalase. In addition, insulin secretion was found to be regulated by alterations in redox state, but not by adipokines. Finally, the effects of the various treatments on activity and mRNA expression of several antioxidant enzymes were determined. Both leptin and adiponectin reduced mRNA levels of superoxide dismutase (SOD)1. Adiponectin also decreased SOD activity and increased catalase and glutathione peroxidase (GPx) activities in the presence of H2O2. The results of this study show that leptin and adiponectin, by inducing a physiological increase in ROS levels, may be positive regulators of beta-cell mass.
authors.affiliation: Department of Molecular Biology, Ariel University Center of Samaria, Ariel, Israel.
authors.forename: Moria
authors.initials: M
authors.lastname: Chetboun
authors.forename: Guila
authors.initials: G
authors.lastname: Abitbol
authors.forename: Konstantin
authors.initials: K
authors.lastname: Rozenberg
authors.forename: Hava
authors.initials: H
authors.lastname: Rozenfeld
authors.forename: Avigail
authors.initials: A
authors.lastname: Deutsch
authors.forename: Sanford R
authors.initials: SR
authors.lastname: Sampson
authors.forename: Tovit
authors.initials: T
authors.lastname: Rosenzweig
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000263:Adenylate Kinase / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D052242:Adiponectin; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C070295:catalase-polyethylene glycol; D011092:Polyethylene Glycols; D002374:Catalase; D005979:Glutathione Peroxidase; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019255:NADPH Oxidases; D058539:Phosphatidylinositol 3-Kinase; D000263:Adenylate Kinase; D000111:Acetylcysteine