Male sex hormones influence sensory neuromodulation of β-cell activity and glucose clearance. Ten-week-old male and female C57BL/6J mice were subjected to gonadectomy (or sham surgery) and then subcutaneously injected with vehicle or capsaicin (50 mg/kg) on three consecutive days into the scruff of the neck. Seven days after sensory chemodenervation, metabolic phenotyping was performed. A. Schematic of the experimental design. B. GTT, C. ITT and D. GSIS in sham male mice. E. GTT, F. ITT and G. GSIS in orchidectomized male mice. H. GTT, I. ITT and J. GSIS in sham female mice. K. GTT, L. ITT and M. GSIS in ovariectomized female mice. Data represent mean ± SEM. ∗p < 0.05, ∗∗p < 0.01 (n = 6–7 per group).