Dataset Information

Isoflurane and Sevoflurane Induce Severe Hepatic Insulin Resistance in a Canine Model.

ABSTRACT:

Introduction

Anesthesia induces insulin resistance, which may contribute to elevated blood glucose and adverse post-operative outcomes in critically ill patients, and impair glycemic control in surgical patients with diabetes. However, little is known about the mechanisms by which anesthesia impairs insulin sensitivity. Here we investigate the effects of anesthesia on insulin sensitivity in metabolic tissues.

Methods

Hyperinsulinemic-euglycemic clamps were performed in 32 lean (control diet; n = 16 conscious versus n = 16 anesthetized) and 24 fat-fed (6 weeks fat-feeding; n = 16 conscious versus n = 8 anesthetized) adult male mongrel dogs in conjunction with tracer methodology to differentiate hepatic versus peripheral insulin sensitivity. Propofol was administered as an intravenous bolus (3mg/kg) to initiate anesthesia, which was then maintained with inhaled sevoflurane or isoflurane (2-3%) for the duration of the procedure.

Results

Anesthesia reduced peripheral insulin sensitivity by approximately 50% in both lean and fat-fed animals as compared to conscious animals, and insulin action at the liver was almost completely suppressed during anesthesia such that hepatic insulin sensitivity was decreased by 75.5% and; 116.2% in lean and fat-fed groups, respectively.

Conclusion

Inhaled anesthesia induces severe hepatic insulin resistance in a canine model. Countermeasures that preserve hepatic insulin sensitivity may represent a therapeutic target that could improve surgical outcomes in both diabetic and healthy patients.

SUBMITTER: Kim SP

PROVIDER: S-EPMC5089720 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Isoflurane and Sevoflurane Induce Severe Hepatic Insulin Resistance in a Canine Model.

Kim Stella P SP Broussard Josiane L JL Kolka Cathryn M CM

PloS one 20161101 11

<h4>Introduction</h4>Anesthesia induces insulin resistance, which may contribute to elevated blood glucose and adverse post-operative outcomes in critically ill patients, and impair glycemic control in surgical patients with diabetes. However, little is known about the mechanisms by which anesthesia impairs insulin sensitivity. Here we investigate the effects of anesthesia on insulin sensitivity in metabolic tissues.<h4>Methods</h4>Hyperinsulinemic-euglycemic clamps were performed in 32 lean (co ...[more]

PMID: 27802272

Similar Datasets

Project description:In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO2) is still permitted for killing rodents according to the Directive 2010/63/EU. Within the scope of refinement, our aim was to investigate if isoflurane and sevoflurane are an appropriate alternative killing method to CO2 in mice. Different concentrations of CO2 (filling rates of 20%, 60%, 100%; CO2 20, 60, 100), isoflurane (Iso 2%, 5%) and sevoflurane (Sevo 4.8%, 8%) were compared in two mouse strains (NMRI, C57Bl/6J) using a broad spectrum of behavioral parameters, including the approach-avoidance test, and analyzing blood for stress parameters (glucose, adrenaline, noradrenaline). We focused in our study on the period from the beginning of the gas inlet to loss of consciousness, as during this period animals are able to perceive pain and distress. Our results show that only higher concentrations of CO2 (CO2 60, 100) and isoflurane (5%) induced surgical tolerance within 300 s in both strains, with CO2 100 being the fastest acting inhalant anesthetic. The potency of halogenated ethers depended on the mouse strain, with C57Bl/6J being more susceptible than NMRI mice. Behavioral analysis revealed no specific signs of distress, e. g. stress-induced grooming, and pain, i. e. audible vocalizations, for all inhalant gases. However, adrenaline and noradrenaline plasma concentrations were increased, especially in NMRI mice exposed to CO2 in high concentrations, whereas we did not observe such increase in animals exposed to isoflurane or sevoflurane. Escape latencies in the approach-avoidance test using C57Bl/6J mice did not differ between the three inhalant gases, however, some animals became recumbent during isoflurane and sevoflurane but not during CO2 exposure. The rise in catecholamine concentrations suggests that CO2 exposure might be linked to a higher stress response compared to isoflurane and sevoflurane exposure, although we did not observe a behavioral correlate for that. Follow-up studies investigating other fast-acting stress hormones and central anxiety circuits are needed to confirm our findings.

Dataset Information

Isoflurane and Sevoflurane Induce Severe Hepatic Insulin Resistance in a Canine Model.

Introduction

Methods

Results

Conclusion

Publications

Isoflurane and Sevoflurane Induce Severe Hepatic Insulin Resistance in a Canine Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets