TRPV1 Mediates Glucose-induced Insulin Secretion Through Releasing Neuropeptides

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_8-37 (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.