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

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 mu M 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 beta-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.