title: Novel Pentapeptide GLP-1 (32-36) Amide Inhibits β-Cell Apoptosis In Vitro and Improves Glucose Disposal in Streptozotocin-Induced Diabetic Mice.
abstract: We proposed that a pentapeptide, LVKGR amide, GLP-1 (32-36) amide, derived from the gluco-incretin hormone, glucagon-like peptide-1 (GLP-1), might possess favorable actions against diabetes. Therefore, GLP-1 (32-36) amide was synthesized and the effects of it were examined in INS-1 cell and streptozotocin-induced diabetic mice model. To determine the protective effects of GLP-1 (32-36) amide on INS-1 cell viability and apoptosis, cells were exposed to 1 μm streptozotocin (STZ) and GLP-1 (32-36) amide for 24 h. Results showed that GLP-1 (32-36) amide treatment decreased apoptosis rate and significantly retained cell viability compared with saline-treated controls. Then, GLP-1 (32-36) amide was administered intraperitoneally to streptozotocin-induced diabetic mice with normal mice used as control. Body weight, energy intake, plasma glucose, and histopathology of the pancreas were assessed. Results showed that GLP-1 (32-36) amide protected β-cell viability and apoptosis against STZ-induced toxicity, inhibited weight gain, and relieved symptoms of polydipsia. Moreover, GLP-1 pentapeptide-treated mice showed a slight trend toward reduced glucose excursions in intraperitoneal glucose tolerance test at the end of the experiment. GLP-1 (32-36) amide exerted favorable protective actions in streptozotocin-induced diabetic mice. The peptide curtailed weight gain and alleviates symptoms of polydipsia. These findings suggested the probable utility of GLP-1 (32-36) amide, a peptide mimetic derived there from GLP-1, for adjuvant treatment of diabetes.
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Lidan
authors.initials: L
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chuandong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Yang
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases and State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D051381:Rats
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C000598373:GLP-1(32-36)amide
keywords: apoptosis; diabetics; glucagon-like peptide-1; metabolite; β-cell