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Nielsen MF, Roelsgaard K, Keiding S, et al. Impaired hepatic counterregulatory response to insulin-induced hypoglycemia in hepatic denervated pigs. J Clin Transl Endocrinol. 2015;2(4):131-136doi: 10.1016/j.jcte.2015.08.004.
Nielsen, M. F., Roelsgaard, K., Keiding, S., Brodersen, K., Møller, N., Vyberg, M., & Vilstrup, H. (2015). Impaired hepatic counterregulatory response to insulin-induced hypoglycemia in hepatic denervated pigs. Journal of clinical & translational endocrinology, 2(4), 131-136. https://doi.org/10.1016/j.jcte.2015.08.004
Nielsen, Michael Festersen, et al. "Impaired hepatic counterregulatory response to insulin-induced hypoglycemia in hepatic denervated pigs." Journal of clinical & translational endocrinology vol. 2,4 (2015): 131-136. doi: https://doi.org/10.1016/j.jcte.2015.08.004
Nielsen MF, Roelsgaard K, Keiding S, Brodersen K, Møller N, Vyberg M, Vilstrup H. Impaired hepatic counterregulatory response to insulin-induced hypoglycemia in hepatic denervated pigs. J Clin Transl Endocrinol. 2015 Sep 25;2(4):131-136. doi: 10.1016/j.jcte.2015.08.004. eCollection 2015 Dec. PMID: 29159118; PMCID: PMC5685012.
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J Clin Transl Endocrinol. 2015 Sep 25;2(4):131-136. doi: 10.1016/j.jcte.2015.08.004. eCollection 2015 Dec.

Impaired hepatic counterregulatory response to insulin-induced hypoglycemia in hepatic denervated pigs.

Journal of clinical & translational endocrinology

Michael Festersen Nielsen, Klaus Roelsgaard, Susanne Keiding, Kathrine Brodersen, Niels Møller, Mogens Vyberg, Hendrik Vilstrup

Affiliations

  1. Department of Surgery, Viborg General Hospital, Denmark.
  2. Departments of Hepatology and Gastroenterology, Aarhus University Hospital, Denmark.
  3. Department of Medicine, Randers General Hospital, Denmark.
  4. Department of Nuclear Medicine & PET Center, Aarhus University Hospital, Denmark.
  5. Department of Medicine M (Endocrinology and Internal Medicine), Aarhus University Hospital, Denmark.
  6. Department of Pathology, Aalborg University Hospital, Denmark.

PMID: 29159118 PMCID: PMC5685012 DOI: 10.1016/j.jcte.2015.08.004

Abstract

OBJECTIVE: The liver reacts to hypoglycemia by increasing its glucose output. This response is assumed to depend both on glucose sensing at the liver and the brain, as well as efferent impulses from the brain to the liver. We tested the importance of this signaling pathway by studying the hepatic response to insulin-induced hypoglycemia in hepatic complete denervated pigs.

MATERIALS/METHODS: Two weeks prior to the metabolic study, 36-kg pigs underwent either total hepatic denervation (DN; n = 12) or sham operation (sham; n = 12). On the metabolic study day, measurements were performed at baseline conditions and during a hypoglycemic hyperinsulinemic (5 mU/kg/min) clamp. Endogenous insulin and glucagon secretions were inhibited by somatostatin, and glucagon was replaced at baseline levels. Endogenous glucose production (EGP) and glucose utilization (Rd) were determined by [3-

RESULTS: Baseline plasma concentrations of glucose, insulin, EGP and Rd did not differ significantly between the two groups of animals. During insulin infusion, the plasma glucose concentration was clamped at ~3 mmol/L in both groups of animals resulting in an increase in plasma concentrations of epinephrine and norepinephrine in sham pigs (both P < 0.05), while this effect was abolished in DN pigs. While insulin action (P = 0.09) and glucose utilization (P = 0.44) were similar, EGP was markedly decreased in the DN pigs (P < 0.05).

CONCLUSION: The findings indicate a blunted hepatic counterregulatory response to hypoglycemia following complete hepatic denervation. This implies that intact neural impulses to and from the liver are necessary to maintain the increase in EGP that protects the organism against hypoglycemia.

Keywords: Counterregulation; DN, denervated pigs; EGP, endogenous glucose production; Endogenous glucose production; Hepatic innervation; Hypoglycemia; Rd, rate of glucose utilization.

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