Kilohertz Frequency Stimulation of Renal Nerves for Modulating Blood Glucose Concentration in Diabetic Rats

Abstract

In recent years, the role of the kidney in glucose homeostasis has gained global interest. The kidneys are innervated by renal nerves, and renal denervation studies to control hypertension have shown improved glucose regulation. We hypothesized that kilohertz frequency stimulation, which can block propagation of action potentials, applied to renal nerves would reduce blood glucose concentration levels by increasing urinary glucose excretion. We performed experiments on 8 anesthetized, streptozotocin-induced diabetic rats. The renal nerves were encircled by a cuff electrode. Blood glucose concentrations were obtained from tail blood samples. Urine glucose concentrations were obtained from bilateral cannulation of the ureters. Electrical stimulation (50 kHz, 15 V) was applied for 60 minutes. The average blood glucose concentration rate was lower during stimulation (−0.78 ± 1.20 mg/dL/min), compared to before stimulation (+1.14 ± 1.83 mg/dL/min; p < 0.05) and after stimulation (+0.63 ± 1.32 mg/dL/min). The average area under the curve for urine glucose concentration was higher during stimulation (7687.4 ± 4006.1 mg/dL) compared to before (6466.9 ± 2772.8 mg/dL) and after stimulation (5277.2 ± 3381.5 mg/dL). Overall, our results show that kilohertz frequency stimulation of renal nerves is a possible approach for the modulation of blood glucose concentration and may introduce an alternative treatment modality for glycemic control in patients with diabetes.