The pancreas is innervated by sensory neurons originating from the vagus and the spinal nerves. A large proportion of these sensory neurons express the transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel. Karam et al. used a combination of chemical and surgical models to address whether TRPV1 sensory neurons directly modulate functional β-cell mass and consequently alter glucose homeostasis. Their data suggest that TRPV1 sensory neurons directly modulate, at least in part, pancreatic β-cell function in a sex-dependent manner.
TRPV1 neurons regulate β-cell function in a sex-dependent manner
Objective: We investigated in male and female mice whether denervation of whole-body or pancreas-projecting TRPV1 sensory neurons regulates adult functional β-cell mass and alters systemic glucose homeostasis.
Methods: We used a combination of pharmacological and surgical approaches to ablate whole-body or pancreatic TRPV1 sensory neurons and assessed islet β-cell function and mass, aspects of glucose and insulin homeostasis, and energy expenditure.
Results: Capsaicin-induced chemodenervation of whole-body TRPV1 sensory neurons improved glucose clearance and enhanced glucose-stimulated insulin secretion without alterations in β-cell proliferation and mass, systemic insulin sensitivity, body composition, and energy expenditure. Similarly, denervation of intrapancreatic TRPV1 afferents by pancreas intraductal injection of capsaicin or surgical removal of the dorsal root ganglia projecting into the pancreas lowered post-absorptive glucose levels and increased insulin release upon glucose stimulation. The beneficial effects of TRPV1 sensory denervation on glucose tolerance and β-cell function were observed in male but not female mice.
Conclusion: Collectively, these findings suggest that TRPV1 neurons regulate glucose homeostasis, at least partly, through direct modulation of glucose-induced insulin secretion and that this regulation operates in a sex-dependent manner.