title: Deuterohemin-AlaHisLys mitigates the symptoms of rats with non-insulin dependent diabetes mellitus by scavenging reactive oxygen species and activating the PI3-K/AKT signal transduction pathway.
abstract: Damage to pancreatic β-cells plays an important role in the development of type 2 diabetes, and oxidative stress is a likely contributor. In the present study, we investigated the effect of deuterohemin-AlaHisLys (DhHP-3), a microperoxidase-11 mimic, on rats with non-insulin dependent diabetes mellitus and examined the action mechanisms of DhHP-3. The induced hyperglycemia, glucose intolerance, and insulin resistance in diabetic rats were associated with increased oxidative stress and damage to pancreatic islets. DhHP-3 (3 mg/kg) ameliorated hyperglycemia and insulin resistance, protected pancreas islet, decreased the content of malondialdehyde, and increased the activity of superoxide dismutase in plasma and pancreatic tissue by reducing ROS levels. Furthermore, DhHP-3 stimulated the proliferation of INS-1 cells and inhibited apoptosis by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3-K/AKT) signaling pathway. Our results demonstrated for the first time that DhHP-3 decreased blood glucose level in rats with non-insulin dependent diabetes mellitus, scavenged reactive oxygen species, activated the PI3-K/AKT signaling pathway, and protected pancreatic β-cells against apoptosis.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, People's Republic of China; School of Life Science, Jilin University, Changchun 130012, People's Republic of China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, People's Republic of China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Lei
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, People's Republic of China; School of Life Science, Jilin University, Changchun 130012, People's Republic of China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, People's Republic of China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29403, USA.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, People's Republic of China; School of Life Science, Jilin University, Changchun 130012, People's Republic of China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, People's Republic of China; School of Life Science, Jilin University, Changchun 130012, People's Republic of China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, People's Republic of China.
authors.forename: Youming
authors.initials: Y
authors.lastname: Guo
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, People's Republic of China; School of Life Science, Jilin University, Changchun 130012, People's Republic of China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, People's Republic of China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, People's Republic of China; School of Life Science, Jilin University, Changchun 130012, People's Republic of China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, People's Republic of China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, People's Republic of China; School of Life Science, Jilin University, Changchun 130012, People's Republic of China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, People's Republic of China; School of Life Science, Jilin University, Changchun 130012, People's Republic of China; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, Jilin University, Changchun 130012, People's Republic of China. Electronic address: wanglp@jlu.edu.cn.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D008297:Male; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D008665:Metalloporphyrins; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C000595463:deuterohemin-AlaHisLys; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
keywords: Deuterohemin-AlaHisLys; Non-insulin dependent diabetes mellitus; PI3-K/AKT pathway; ROS