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Hyperinsulinaemic hypoglycaemia in non-anaesthetized Göttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes

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Lyhne, Mille K ; Vegge, Andreas ; Povlsen, Gro Klitgaard ; Slaaby, Rita ; Kildegaard, Jonas ; Pedersen-Bjergaard, Ulrik ; Olsen, Lisbeth H. / Hyperinsulinaemic hypoglycaemia in non-anaesthetized Göttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes. I: Scientific Reports. 2021 ; Bind 11, Nr. 1. s. 5983.

Bibtex

@article{f9df5a2923bd42bc9b4022673d63f0a4,
title = "Hyperinsulinaemic hypoglycaemia in non-anaesthetized G{\"o}ttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes",
abstract = "The potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8-1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.",
author = "Lyhne, {Mille K} and Andreas Vegge and Povlsen, {Gro Klitgaard} and Rita Slaaby and Jonas Kildegaard and Ulrik Pedersen-Bjergaard and Olsen, {Lisbeth H}",
year = "2021",
month = mar,
day = "16",
doi = "10.1038/s41598-021-84758-w",
language = "English",
volume = "11",
pages = "5983",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Hyperinsulinaemic hypoglycaemia in non-anaesthetized Göttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes

AU - Lyhne, Mille K

AU - Vegge, Andreas

AU - Povlsen, Gro Klitgaard

AU - Slaaby, Rita

AU - Kildegaard, Jonas

AU - Pedersen-Bjergaard, Ulrik

AU - Olsen, Lisbeth H

PY - 2021/3/16

Y1 - 2021/3/16

N2 - The potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8-1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.

AB - The potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8-1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.

U2 - 10.1038/s41598-021-84758-w

DO - 10.1038/s41598-021-84758-w

M3 - Journal article

C2 - 33727615

VL - 11

SP - 5983

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -

ID: 64351037