Abstract
Background and Aims
Bioelectronic medicine aims to provide real-time and patient-specific therapies to diabetes through recording and modulation of peripheral nerves to improve glycemic fluctuations. This pilot study investigates the impact of stimulation frequency on pancreatic secretion and glucose homeostasis.
Methods
Acute bipolar stimulation (biphasic charge-balanced square pulses, 1.75mA amplitude, 0.5ms pulse width) was applied to the intact left cervical vagus nerve in fasted anesthetized healthy Wistar rats. The impact of two stmulation frequencies was studied (5Hz, 10Hz). Blood glucose, and insulin and glucagon serum concentrations were measured and compared with a control group during baseline (15 min), stimulation (20 min) and post-stimulation (50 min).
Results
Both frequencies resulted in an immediate and sustained increase in glucose levels, the highest frequency showing the greatest percentage of change over baseline (5Hz-stim: 41.3±13.7%; 10Hz-stim: 56.27±13.9%). In neither case this increase was accompanied by a meaningful change in insulin (5Hz-stim: 3.02±0.53ng/mL baseline, 3.13±0.48 ng/mL stimulation; 10Hz-stim: 2.53±0.32ng/mL baseline, 2.57±0.13ng/mL stimulation). Glucagon levels exhibited a decrease during the 10Hz-stim period (1.51±0.04pg/mL baseline, 1.10±0.12pg/mL stimulation), which was not observed in the 5Hz-stim (1.57±0.06pg/mL baseline, 1.50±0.06pg/mL stimulation). In the control group, neither the glucose concentration (change over baseline 1.48±8.61%) nor the insulin (2.98±0.14ng/mL baseline, 3.04±0.11ng/mL sham-stimulation) changed meaningfully during sham-stimulation. Glucagon concentration, however, was reduced (1.50±0.13pg/mL baseline, 1.26±0.14pg/mL sham-stimulation).
Conclusions
These results suggest that the rise in glucose levels after stimulation is mediated by an increase of hepatic glucose release. They also motivate the development of new artificial pancreas that incorporate control of the neural signals for optimal glucose management.
