1.Glucagon responses to exercise-induced hypoglycaemia are improved by somatostatin receptor type 2 antagonism in a rat model of diabetes.
Leclair E1, Liggins RT2, Peckett AJ1, Teich T1, Coy DH3, Vranic M4, Riddell MC5. Diabetologia. 2016 Apr 13. [Epub ahead of print]
AIMS/HYPOTHESIS: Regular exercise is at the cornerstone of care in type 1 diabetes. However, relative hyperinsulinaemia and a blunted glucagon response to exercise promote hypoglycaemia. Recently, a selective antagonist of somatostatin receptor 2, PRL-2903, was shown to improve glucagon counterregulation to hypoglycaemia in resting streptozotocin-induced diabetic rats. The aim of this study was to test the efficacy of PRL-2903 in enhancing glucagon counterregulation during repeated hyperinsulinaemic exercise.
2.Glucoregulatory, endocrine and morphological effects of [P5K]hymenochirin-1B in mice with diet-induced glucose intolerance and insulin resistance.
Owolabi BO1, Ojo OO1,2, Srinivasan DK1, Conlon JM3, Flatt PR1, Abdel-Wahab YH1. Naunyn Schmiedebergs Arch Pharmacol. 2016 Apr 12. [Epub ahead of print]
The frog skin host-defence peptide hymenochirin-1B has been shown to stimulate insulin release in vitro from isolated pancreatic islets and BRIN-BD11 clonal β-cells. This study examines the effects of 28-day administration of a more potent analogue [P5K]hymenochirin-1B ([P5K]hym-1B) (75 nmol·kg-1 body weight) to high-fat-fed mice with obesity, glucose intolerance and insulin resistance. Treatment with [P5K]hym-1B significantly decreased plasma glucose concentrations and improved glucose tolerance, insulin secretion, insulin sensitivity and increased the magnitude of the incretin effect (difference in response to oral vs intraperitoneal glucose loads). Responses to established insulin secretagogues were greater in islets isolated from treated animals compared with saline-treated controls. [P5K]hym-1B administration significantly decreased total islet area and β- and α-cell areas, and resulted in lower concentrations of circulating triglycerides and plasma and pancreatic glucagon.
3.Neuroprotective role of (Val(8))GLP-1-Glu-PAL in an in vitro model of Parkinson's disease.
Li L1, Liu K1, Zhao J1, Holscher C2, Li GL3, Liu YZ3. Neural Regen Res. 2016 Feb;11(2):326-31. doi: 10.4103/1673-5374.177742.
The growth factor glucagon-like peptide-1 (GLP-1) is neuroprotective in several animal models of neurodegeneration. Here, we analyzed the neuroprotective effects of a novel protease-resistant GLP-1 analogue, (Val(8))GLP-1-Glu-PAL, which has advantages over older analogues, such as improvement of hippocampal neurogenesis, glucose homeostasis, and insulin secretion. We established an in vitro model of Parkinson's disease using the mitochondrial stressor rotenone in primary cultured mouse neurons pretreated with (Val(8))GLP-1-Glu-PAL. (Val(8))GLP-1-Glu-PAL alone did not affect neuronal viability, but prevented the rotenone-induced reduction in cell viability in a dose-dependent manner. In addition, (Val(8))GLP-1-Glu-PAL pretreatment prevented rotenone-induced proapoptotic changes manifesting as downregulation of procaspase-3 and Bcl-2 and upregulation of cleaved caspase-3. These results demonstrate that the novel agent (Val(8))GLP-1-Glu-PAL shows promise as a drug treatment for Parkinson's disease.
