Effect of Low-Frequency Renal Nerve Stimulation on Renal Glucose Release during Normoglycemia and a Hypoglycemic Clamp in Pigs

Author:

Nistor Marius1ORCID,Schmidt Martin2ORCID,Klingner Carsten3ORCID,Klingner Caroline3,Matziolis Georg1,Shayganfar Sascha45,Schiffner René1456ORCID

Affiliation:

1. Orthopaedic Department, Jena University Hospital, 07747 Jena, Germany

2. Institute for Biochemistry II, Jena University Hospital, 07747 Jena, Germany

3. Department of Neurology, Jena University Hospital, 07747 Jena, Germany

4. Emergency Department, Helios University Clinic Wuppertal, 42283 Wuppertal, Germany

5. Faculty of Health/School of Medicine, Lehrstuhl für Klinische Akut- und Notfallmedizin, Witten/Herdecke University, Alfred-Herrhausen-Straße 50, 58448 Witten, Germany

6. Emergency Department, Otto-von-Guericke University, 39120 Magdeburg, Germany

Abstract

Previously, we demonstrated that renal denervation in pigs reduces renal glucose release during a hypoglycemic episode. In this study we set out to examine changes in side-dependent renal net glucose release (SGN) through unilateral low-frequency stimulation (LFS) of the renal plexus with a pulse generator (2–5 Hz) during normoglycemia (60 min) and insulin-induced hypoglycemia ≤3.5 mmol/L (75 min) in seven pigs. The jugular vein, carotid artery, renal artery and vein, and both ureters were catheterized for measurement purposes, blood pressure management, and drug and fluid infusions. Para-aminohippurate (PAH) and inulin infusions were used to determine side-dependent renal plasma flow (SRP) and glomerular filtration rate (GFR). In a linear mixed model, LFS caused no change in SRP but decreased sodium excretion (p < 0.0001), as well as decreasing GFR during hypoglycemia (p = 0.0176). In a linear mixed model, only hypoglycemic conditions exerted significant effects on SGN (p = 0.001), whereas LFS did not. In a Wilcoxon signed rank exact test, LFS significantly increased SGN (p = 0.03125) and decreased sodium excretion (p = 0.0017) and urinary flow rate (p = 0.0129) when only considering the first instance LFS followed a preceding period of non-stimulation during normoglycemia. To conclude, this study represents, to our knowledge, the first description of an induction of renal gluconeogenesis by LFS.

Funder

German Research Foundation

Open Access Publication Fund of the Thueringer Universitaets- und Landesbibliothek Jena

Publisher

MDPI AG

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