title: Isoflurane and Sevoflurane Induce Severe Hepatic Insulin Resistance in a Canine Model.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, United States of America.
authors: Stella P
authors: SP
authors: Kim
authors: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, United States of America.
authors: Josiane L
authors: JL
authors: Broussard
authors: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, United States of America.
authors: Cathryn M
authors: http://orcid.org/0000-0002-6636-7062
authors: CM
authors: Kolka
mesh_terms: D000769:Anesthesia, Inhalation / Q000009:adverse effects; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage; D004285:Dogs; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000379:methods; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D007530:Isoflurane / Q000009:adverse effects*; D008099:Liver / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000009:adverse effects*; D015742:Propofol / Q000009:adverse effects; D000077149:Sevoflurane
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane; D005947:Glucose; D015742:Propofol