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TRPV1 neurons regulate β-cell function in a sex-dependent manner
- Source :
- Molecular Metabolism, Molecular Metabolism, Vol 18, Iss, Pp 60-67 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier, 2018.
-
Abstract
- There is emerging evidence to support an important role for the transient receptor potential vanilloid type 1 (TRPV1) sensory innervation in glucose homeostasis. However, it remains unknown whether the glucoregulatory action of these afferent neurons is sex-biased and whether it is pancreatic β-cell-mediated. 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.<br />Highlights • Whole-body ablation of TRPV1 neurons increases insulin secretion and glucose clearance in male but not female mice. • Pancreas-selective ablation of TRPV1 neurons enhances insulin secretion and glucose clearance in male but not female mice. • Surgical removal of lower thoracic DRGs improves insulin secretion and glucose clearance in male but not female mice.
- Subjects :
- 0301 basic medicine
Blood Glucose
Male
lcsh:Internal medicine
medicine.medical_specialty
β-cell function
medicine.medical_treatment
TRPV1
TRPV Cation Channels
Sensory system
Glucose homeostasis
03 medical and health sciences
Transient receptor potential channel
Mice
Sex Factors
Internal medicine
Insulin-Secreting Cells
medicine
Animals
Homeostasis
Neurons, Afferent
lcsh:RC31-1245
Molecular Biology
Denervation
TRPV1 sensory innervation
business.industry
Insulin
Cell Biology
Sex difference
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Endocrinology
nervous system
Original Article
Female
Pancreas
business
Energy Metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 22128778
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Molecular Metabolism
- Accession number :
- edsair.doi.dedup.....cbd3b4ad73638bb651bad7d1f8e90fd6