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other·preclinical research, endocrinology, nephrology, biomedical research·PMC10454812

Renal Glucose Release after Unilateral Renal Denervation during a Hypoglycemic Clamp in Pigs with an Altered Hypothalamic Pituitary Adrenal Axis after Late-Gestational Dexamethasone Injection

International Journal of Molecular Sciences · 9 authors, 7 centres

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TL;DR

This preclinical study in pigs with a prenatal dexamethasone-induced altered hypothalamic-pituitary-adrenal axis (HPAA) found that unilateral renal denervation reduced renal glucose release during hypoglycaemia, but the effect was only half as large as previously observed in animals without an altered HPAA.

Full summary

570 CHARS

Nine pigs whose mothers received late-gestational dexamethasone injections underwent a hyperinsulinaemic–hypoglycaemic clamp (<3 mmol/L for 75 min) after unilateral surgical renal denervation. Side-dependent renal net glucose release (SGN) was measured. Renal denervation resulted in a significant 25 ± 23% decrease in SGN compared to the non-denervated side (p = 0.004). Urinary sodium excretion significantly increased with denervation (p = 0.019). Measures of renal haemodynamics, including plasma flow and glomerular filtration rate, were not altered by denervation.

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other

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preclinical research

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ORIGINAL PAPER

PMC10454812

Renal Glucose Release after Unilateral Renal Denervation during a Hypoglycemic Clamp in Pigs with an Altered Hypothalamic Pituitary Adrenal Axis after Late-Gestational Dexamethasone Injection

International Journal of Molecular Sciences

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ABSTRACT

Previously, we demonstrated in pigs that renal denervation halves glucose release during hypoglycaemia and that a prenatal dexamethasone injection caused increased ACTH and cortisol concentrations as markers of a heightened hypothalamic pituitary adrenal axis (HPAA) during hypoglycaemia. In this study, we investigated the influence of an altered HPAA on renal glucose release during hypoglycaemia. Pigs whose mothers had received two late-gestational dexamethasone injections were subjected to a 75 min hyperinsulinaemic–hypoglycaemic clamp (<3 mmol/L) after unilateral surgical denervation. Para-aminohippurate (PAH) clearance, inulin, sodium excretion and arterio–venous blood glucose difference were measured every fifteen minutes. The statistical analysis was performed with a Wilcoxon signed-rank test. PAH, inulin, the calculated glomerular filtration rate and plasma flow did not change through renal denervation. Urinary sodium excretion increased significantly ( p = 0.019). Side-dependent renal net glucose release (SGN) decreased by 25 ± 23% ( p = 0.004). At 25 percent, the SGN decrease was only half of that observed in non-HPAA-altered animals in our prior investigation. The current findings may suggest that specimens with an elevated HPAA undergo long-term adaptations to maintain glucose homeostasis. Nonetheless, the decrease in SGN warrants further investigations and potentially caution in performing renal denervation in certain patient groups, such as diabetics at risk of hypoglycaemia.

CITATION EXPORT

Marius Nistor, Martin Schmidt, Carsten Klingner et al.. Renal Glucose Release after Unilateral Renal Denervation during a Hypoglycemic Clamp in Pigs with an Altered Hypothalamic Pituitary Adrenal Axis after Late-Gestational Dexamethasone Injection. International Journal of Molecular Sciences. (2023). https://doi.org/10.3390/ijms241612738

AUTHORS

9 · 7 CENTRES

Marius Nistor, Martin Schmidt, Carsten Klingner, Caroline Klingner, Matthias Schwab, Sabine Juliane Bischoff, Georg Matziolis, Guadalupe Leticia Rodríguez-González, René Schiffner

1Orthopaedic Department, Jena University Hospital, Campus Eisenberg, 07607 Eisenberg, Germany; [email protected] (M.N.);
2Institute for Biochemistry II, Jena University Hospital, 07743 Jena, Germany
3Department of Neurology, Jena University Hospital, 07747 Jena, [email protected] (M.S.)
4Institute for Laboratory Animals and Welfare, Jena University Hospital, 07743 Jena, Germany
5Reproductive Biology, National Institute of Medical Science and Nutrition, 14080 Mexico City, Mexico
6Emergency Department, Otto-von-Guericke University, 39120 Magdeburg, Germany
7Emergency Department, Helios University Clinic Wuppertal, 42283 Wuppertal, Germany

EDITOR / REVIEWER

Yutang Wang, Kate Denton