1. Academic Validation
  2. Novel Pentapeptide GLP-1 (32-36) Amide Inhibits β-Cell Apoptosis In Vitro and Improves Glucose Disposal in Streptozotocin-Induced Diabetic Mice

Novel Pentapeptide GLP-1 (32-36) Amide Inhibits β-Cell Apoptosis In Vitro and Improves Glucose Disposal in Streptozotocin-Induced Diabetic Mice

  • Chem Biol Drug Des. 2015 Dec;86(6):1482-90. doi: 10.1111/cbdd.12615.
Lidan Sun 1 Yuxuan Dai 1 Chuandong Wang 2 Yingying Chu 1 Xin Su 1 Jianyong Yang 1 Jie Zhou 1 Wenlong Huang 1 Hai Qian 1
Affiliations

Affiliations

  • 1 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.
  • 2 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.
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.

Keywords

apoptosis; diabetics; glucagon-like peptide-1; metabolite; β-cell.

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