Department of Physiology, Hanlin College, Nanjing University of Chinese Medicine, Taizhou 225300, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou 225001, China.
College of Physical Education, Anhui Normal University, Wuhu 241003, China.
Biochem Pharmacol. 2018 Oct;156:241-247. doi: 10.1016/j.bcp.2018.08.036. Epub 2018 Aug 29.
Although recent results of our and other studies have showed that galanin (GAL) is an antidiabetic and anti-inflammatory neuropeptide, the molecular mechanism how central GAL regulates energy homeostasis and insulin sensitivity is still not fully understood. The aim of this study was to investigate whether central type 2 of GAL receptors (GALR2) are involved in the regulation of systemic glucose metabolism and its underlying mechanisms. In the present study, type 2 diabetic rats were intracerebroventricularly (i.c.v.) given 100 nM/kg/d GALR2 agonist M1145 or GALR2 antagonist M871 in 5 μl artificial cerebrospinal fluid once a day for consecutive 21 days. Then insulin resistance indexes, inflammatory factor and many genes associated with the function of glucose metabolism were examined in peripheral tissues. The present findings showed that the intracerebroventricular injection of M1145 or M871 respectively increased or decreased glucose infusion rates in hyperinsulinemic euglycemic clamp tests, but attenuated or enhanced the plasma inflammatory factors and glucose concentration in type 2 diabetic rats. Moreover, administration of M1145 markedly increased PGC-1α and GLUT4 expression in skeletal muscles and adipocytes of type 2 diabetic rats. In conclusion, activation of central GALR2 promotes glucose metabolism and ameliorates insulin resistance mainly through the PGC-1α/GLUT4 pathways. The central GALR2 is crucial to whole-body insulin sensitivity and energy homeostasis.
尽管我们和其他研究最近的结果表明甘丙肽（GAL）是一种抗糖尿病和抗炎神经肽，但中枢 GAL 如何调节能量平衡和胰岛素敏感性的分子机制仍不完全清楚。本研究旨在探讨中枢型 2 型甘丙肽受体（GALR2）是否参与全身葡萄糖代谢的调节及其潜在机制。在本研究中，2 型糖尿病大鼠连续 21 天每天 1 次通过侧脑室（i.c.v.）给予 100nM/kg/d GALR2 激动剂 M1145 或 GALR2 拮抗剂 M871，剂量均为 5μl 人工脑脊液。然后在周围组织中检查胰岛素抵抗指标、炎症因子和许多与葡萄糖代谢功能相关的基因。本研究结果表明，侧脑室注射 M1145 或 M871 分别增加或降低高胰岛素正常血糖钳夹试验中的葡萄糖输注率，但减轻或增强 2 型糖尿病大鼠的血浆炎症因子和葡萄糖浓度。此外，M1145 的给药显著增加了 2 型糖尿病大鼠骨骼肌和脂肪细胞中 PGC-1α 和 GLUT4 的表达。总之，中枢 GALR2 的激活通过 PGC-1α/GLUT4 途径促进葡萄糖代谢并改善胰岛素抵抗。中枢 GALR2 对全身胰岛素敏感性和能量平衡至关重要。
