• Emiliano Fratini, Emanuela Pasquali, Maria Luisa Grilli, Marta Piscitelli, Alessandro Zambotti, Mariateresa Mancuso, Caterina Merla, and Silvia Bossi.
• Laboratory of Red Biotechnologies, Division of Biotechnologies, Italian National Agency for New Technologies, Energy and Sustainable Economic Development, Casaccia Research Center, Roma, Italy.
• Neuromodulation. 2024 Nov 29.

ObjectivesThis study introduces EMPATIC (Electro-Modulation of PAncreaTic Islet Cells), a miniaturized intraneural device designed for transversal insertion into small nerves with a mean diameter of 400 μm. EMPATIC aims to modulate glucose tolerance through intraneural vagus nerve stimulation (VNS) in rats.Materials And MethodsEMPATIC design was optimized to fit into the cervical vagus nerve of rats and was developd through thin film microtechnologies. We evaluated the efficacy of the stimulation protocol (200 μA for 10 μs at 1 Hz) on glucose tolerance after intraperitoneal injection of glucose in three rat groups: control (no implant), sham (EMPATIC implant, no stimulation), and VNS (EMPATIC implant with stimulation).ResultsEMPATIC treatment in the VNS group significantly affected glucose tolerance tests compared with control and sham groups. The glucose tolerance test's area under the curve was 17,652 ± 913 mg∗min/dL in the control group, 16,929 ± 765 mg∗min/dL in the sham group, and reduced to 12,749 ± 1,075 mg∗min/dL in the stimulated group with statistical significance (p < 0.05 stimulated vs sham group, p < 0.05 stimulated vs control group). Blood glucose and insulin levels were measured, also under fasting conditions, for control and VNS groups, producing no statistically significant difference.ConclusionsEMPATIC treatment is effective in hyperglycemic conditions after glucose intake. No significant effects were observed when VNS was applied under fasting conditions. This study indicated the suitability of applying thin-film intrafascicular electrodes for transversal insertion into small nerves (mean diameter of 400 μm), which, to the best of our knowledge, represents an advancement over the state of the art. It also establishes the feasibility of investigating neural pathways related to glucose homeostasis using invasive intraneural electrodes in the right cervical vagus nerve of rats.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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