title: Renal glucose release during hypoglycemia is partly controlled by sympathetic nerves - a study in pigs with unilateral surgically denervated kidneys.
abstract: Catecholamines are known to increase renal glucose release during hypoglycemia. The specific extent of the contribution of different sources of catecholamines, endocrine delivery via circulation or release from autonomous sympathetic renal nerves, though, is unknown. We tested the hypothesis that sympathetic renal innervation plays a major role in the regulation of renal gluconeogenesis. For this purpose, instrumented adolescent pigs had one kidney surgically denervated while the other kidney served as a control. A hypoglycemic clamp with arterial blood glucose below 2 mmol/L was maintained for 75 min. Arteriovenous blood glucose difference, inulin clearance, p-aminohippurate clearance, and sodium excretion were measured in intervals of 15 min separately for both kidneys. Blood glucose was lowered to 0.84 ± 0.33 mmol/L for 75 min. The side-dependent renal net glucose release (SGN) decreased significantly after the unilateral ablation of renal nerves. In the linear mixed model, renal denervation had a significant inhibitory effect on renal net glucose release (P = 0.036). The SGN of the ablated kidney decreased by 0.02 mmol/min and was equivalent to 43.3 ± 23.2% of the control (nonablated) kidney in the pigs. This allows the conclusion that renal glucose release is partly controlled by sympathetic nerves. This may be relevant in humans as well, and could explain the increased risk of severe hypoglycemia of patients with diabetes mellitus and autonomous neuropathy. The effects of denervation on renal glucose metabolism should be critically taken into account when considering renal denervation as a therapy in diabetic patients.
authors.affiliation: Institute for Laboratory Animals and Welfare, Jena University Hospital, Jena, Germany.
authors.forename: Sabine J
authors.initials: SJ
authors.lastname: Bischoff
authors.affiliation: Institute for Biochemistry II, Jena University Hospital, Jena, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Institute of Medical Statistics, Computer Sciences and Documentation Science, Jena University Hospital, Jena, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehmann
authors.affiliation: Department of Neurology, Jena University Hospital, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
authors.affiliation: Orthopaedic Department, Jena University Hospital, Jena, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Matziolis
authors.affiliation: Department of Internal Medicine II, Helios Hospital, Erfurt, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Saemann
authors.affiliation: Department of Neurology, Jena University Hospital, Jena, Germany Orthopaedic Department, Jena University Hospital, Jena, Germany rene.schiffner@med.uni-jena.de.
authors.forename: René
authors.initials: R
authors.lastname: Schiffner
keywords: Glucose release; hypoglycemia; renal denervation; side dependent