title: Anti-diabetic properties of a non-conventional radical scavenger, as compared to pioglitazone and exendin-4, in streptozotocin-nicotinamide diabetic mice.
abstract: We previously showed that the innovative radical scavenger bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) improves metabolic dysfunctions in a diabetic mouse model. Here, we compared the in vivo effects of IAC with those of the anti-diabetic drugs pioglitazone (PIO) and exendin-4 (EX-4). Diabetes was induced in C57Bl/6J mice by streptozotocin and nicotinamide administration. Paralleled by healthy controls, diabetic animals (D) were randomly assigned to four groups and treated daily for 7 consecutive weeks: D+saline, ip; D+IAC 30mg/kgb.w., ip; D+PIO 10mg/kgb.w. per os; and D+EX-4, 50μg/kgb.w., ip. Our results show that IAC reduced basal hyperglycemia and improved glucose tolerance better than PIO or EX-4. Interestingly, in the heart of diabetic mice, IAC treatment normalized the increased levels of GSSG/GSH ratio and thiobarbituric acid reactive substances, indexes of oxidative stress and damage, while PIO and EX-4 were less effective. As supported by immunohistochemical data, IAC markedly prevented diabetic islet β-cell reduced density, differently from PIO and EX-4 that had only a moderate effect. Interestingly, in diabetic animals, IAC treatment enhanced the activity of pancreatic-duodenal homeobox 1 (PDX-1), an oxidative stress-sensitive transcription factor essential for maintenance of β-cell function, as evaluated by quantification of its nuclear immunostaining, whereas PIO or EX-4 treatments did not. Altogether, these observations support the improvement of the general redox balance and β-cell function induced by IAC treatment in streptozotocin-nicotinamide diabetic mice. Furthermore, in this model, the correction of diabetic alterations was better obtained by treatment with the radical scavenger IAC than with pioglitazone or exendin-4.
authors: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
authors: Michela
authors: M
authors: Novelli
authors: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors: Donatella
authors: D
authors: Canistro
authors: Medestea Research, Via Cernaia 31, 10121 Torino, Italy.
authors: Manuela
authors: M
authors: Martano
authors: Department of Surgical, Medical, Molecular, and Critical Area Pathology, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors: Niccola
authors: N
authors: Funel
authors: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors: Andrea
authors: A
authors: Sapone
authors: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors: Simone
authors: S
authors: Melega
authors: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
authors: Matilde
authors: M
authors: Masini
authors: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy.
authors: Vincenzo
authors: V
authors: De Tata
authors: Institute of Clinical Physiology, CNR, Via Moruzzi 1, 56124 Pisa, Italy.
authors: Anna
authors: A
authors: Pippa
authors: Institute of Clinical Physiology, CNR, Via Moruzzi 1, 56124 Pisa, Italy.
authors: Cecilia
authors: C
authors: Vecoli
authors: Department of Surgical, Medical, Molecular, and Critical Area Pathology, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
authors: Daniela
authors: D
authors: Campani
authors: Medestea Research, Via Cernaia 31, 10121 Torino, Italy.
authors: Rocco
authors: R
authors: De Siena
authors: Medestea Research, Via Cernaia 31, 10121 Torino, Italy.
authors: Antonio
authors: A
authors: Soleti
authors: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors: Moreno
authors: M
authors: Paolini
authors: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy. Electronic address: pellegrino.masiello@med.unipi.it.
authors: Pellegrino
authors: P
authors: Masiello
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D000077270:Exenatide; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009536:Niacinamide / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D000077205:Pioglitazone; D011897:Random Allocation; D013311:Streptozocin / Q000633:toxicity; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D016166:Free Radical Scavengers; D007004:Hypoglycemic Agents; D010455:Peptides; D045162:Thiazolidinediones; D014688:Venoms; D009536:Niacinamide; D013311:Streptozocin; D000077270:Exenatide; D000077205:Pioglitazone
keywords: Exendin-4; Oxidative stress; PDX-1; Pioglitazone; Radical scavengers; Type 2 diabetes mellitus; bis(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate; exendin-4; pioglitazone