title: Protamine zinc insulin combined with sodium selenite improves glycometabolism in the diabetic KKAy mice.
abstract: Long-term, high dosage protamine zinc insulin (PZI) treatments produce adverse reactions. The trace element selenium (Se) is a candidate for the prevention of diabetes due to anti-oxidative stress activity and the regulation of glycometabolism. In this study, we aimed to investigate the anti-diabetic effects of a combination of PZI and Se on type 2 diabetes. Diabetic KKAy mice were randomized into the following groups: model group and groups that were subcutaneously injected with PZI, Se, high or low dose PZI + Se for 6 weeks. PZI combined with Se decreased the body weight and fasting blood glucose levels. Moreover, this treatment also improved insulin tolerance, as determined by the reduced values from the oral glucose tolerance test and insulin tolerance test, and increased insulin levels and insulin sensitivity index. PZI combined with Se ameliorated skeletal muscle and β-cell damage and the impaired mitochondrial morphology. Oxidative stress was also reduced. Furthermore, PZI combined with Se upregulated phosphatidylinositol 3-kinase (PI3K) and downregulated protein tyrosine phosphatase 1B (PTP1B). Importantly, the low dosage combination produced effects similar to PZI alone. In conclusion, PZI combined with Se improved glycometabolism and ameliorated the tissue and mitochondrial damage, which might be associated with the PI3K and PTP1B pathways.
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.|Xi'an No. 1 Hospital, Xi'an 710002, Shaanxi, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.|Taizhou People's Hospital, Taizhou 225300, Jiangsu, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.|Department of Pharmacy, 302 Military Hospital of China, Beijing 100039, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Yan
authors.affiliation: Electron Microscopy Room, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.
authors.forename: Bingxiang
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Electron Microscopy Room, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, Shaanxi, China.|Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, Shaanxi, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007336:Insulin, Isophane / Q000008:administration & dosage* / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D018038:Sodium Selenite / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D007336:Insulin, Isophane; D018038:Sodium Selenite