Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential therapeutic approach for type 2 diabetes

• DOI: 10.1007/s00125-017-4533-7
• Publication Date: 2018-01-11T16:11:55Z
• Authors: Joana F. Sacramento; Daniel J. Chew; Bernardete F. Melo; Matteo Donegá; Wesley Dopson; Maria P. Guarino; Alison Robinson; Jesus Prieto-Lloret; Sonal Patel; Bradley J. Holinski; Nishan Ramnarain; Victor Pikov; Kristoffer Famm; Silvia V. Conde
• Keywords: Insulin tolerance test

A new class of treatments termed bioelectronic medicines are now emerging that aim to target individual nerve fibres or specific brain circuits in pathological conditions repair lost function and reinstate a healthy balance. Carotid sinus (CSN) denervation has been shown improve glucose homeostasis insulin-resistant glucose-intolerant rats; however, these positive effects from surgery appear diminish over time heavily caveated by the severe adverse associated with permanent loss chemosensory function. Herein we characterise ability novel application, classified as kilohertz frequency alternating current (KHFAC) modulation, suppress neural signals within CSN rodents.Rats were fed either chow high-fat/high-sucrose (HFHSu) diet (60% lipid-rich plus 35% sucrose drinking water) 14 weeks. Neural interfaces bilaterally implanted CSNs attached an external pulse generator. The rats then randomised KHFAC sham modulation groups. variables defined acutely respiratory cardiac responses hypoxia (10% O2 + 90% N2). Insulin sensitivity was evaluated periodically through ITT tolerance OGTT.KHFAC CSN, applied 9 weeks, restored insulin (constant test [KITT] HFHSu sham, 2.56 ± 0.41% glucose/min; KITT KHFAC, 5.01 0.52% glucose/min) (AUC 1278 20.36 mmol/l × min; AUC 1054.15 62.64 min) rat models type 2 diabetes. Upon cessation resistance intolerance returned normal values 5 weeks.KHFAC improves metabolic control These outcomes have significant translational potential therapeutic modality for purpose treating diseases humans.