Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, MI, U.S.A.
Neuroscience Program, Michigan State University, East Lansing, MI, U.S.A.
In Vivo. 2019 Sep-Oct;33(5):1431-1437. doi: 10.21873/invivo.11621.
BACKGROUND/AIM: Transient receptor potential vanilloid 1 (TRPV1)-expressing sensory nerves innervate the pancreatic islets. Sensory neuropeptides, including calcitonin gene-related peptide (CGRP) and substance P (SP), participate in insulin secretion. This study aimed to investigate the role of TRPV1 in glucose-induced insulin secretion.
TRPV1 and wild-type (WT) mice were fed a normal diet for 24 weeks. Glucose tolerance and insulin secretion were measured at the end of the experiments.
TRPV1 mice had greater impairments in glucose tolerance and higher decrease in glucose-induced insulin secretion than WT mice. Capsaicin (a TRPV1 agonist) increased insulin secretion in WT, but not in TRPV1 mice. Glucose-induced insulin secretion was blunted in TRPV1 mice, and was attenuated by AMG9810 (a TRPV1 inhibitor), CGRP (a CGRP receptor antagonist), or RP67580 (a NK-1 receptor antagonist) in WT mice. Glucose-induced SP and CGRP release from WT pancreas was higher than that from TRPV1 pancreas.
TRPV1 mediates glucose-induced insulin secretion likely through CGRP and SP release.
背景/目的:表达瞬时受体电位香草酸 1 型(TRPV1)的感觉神经支配胰岛。感觉神经肽,包括降钙素基因相关肽(CGRP)和 P 物质(SP),参与胰岛素分泌。本研究旨在探讨 TRPV1 在葡萄糖诱导的胰岛素分泌中的作用。
TRPV1 和野生型(WT)小鼠分别用正常饮食喂养 24 周。实验结束时测量葡萄糖耐量和胰岛素分泌。
TRPV1 小鼠的葡萄糖耐量受损程度大于 WT 小鼠,葡萄糖诱导的胰岛素分泌减少程度也更高。辣椒素(TRPV1 激动剂)增加 WT 小鼠的胰岛素分泌,但不增加 TRPV1 小鼠的胰岛素分泌。TRPV1 小鼠的葡萄糖诱导胰岛素分泌减弱,而在 WT 小鼠中,AMG9810(TRPV1 抑制剂)、CGRP(CGRP 受体拮抗剂)或 RP67580(NK-1 受体拮抗剂)均可减弱该作用。WT 胰腺中葡萄糖诱导的 SP 和 CGRP 释放量高于 TRPV1 胰腺。
TRPV1 通过 CGRP 和 SP 的释放介导葡萄糖诱导的胰岛素分泌。