title: Insulin decreases isoflurane minimum alveolar anesthetic concentration in rats independently of an effect on the spinal cord.
abstract: The observation that insulin supplies an element of analgesia suggests that insulin administration might decrease the concentration of inhaled anesthetic required to produce MAC (the minimum alveolar anesthetic concentration required to eliminate movement in response to noxious stimulation in 50% of subjects). We hypothesized that insulin decreases MAC by directly affecting the nervous system, by decreasing blood glucose, or both. To test these hypotheses, we infused increasing doses of insulin either intrathecally or IV in rats anesthetized with isoflurane and determined the resulting MAC change (assessing forelimb and hindlimb movement separately). Infusion of insulin produced a dose-related decrease in MAC that did not differ among groups. That is, the IV and intrathecal infusions caused similar decreases in MAC at a given infusion rate. Blood glucose concentrations were larger in the rats given insulin with 5% dextrose. However, the percentage change in MAC determined from forelimb versus hindlimb movement did not differ. For a given insulin infusion rate, MAC changes and glucose levels did not correlate with each other, except, possibly, for the most rapid infusion rate, for which smaller glucose concentrations were associated with a marginally larger decrease in MAC. Intrathecal infusions of insulin did not produce spinal cord injury. In summary, we found that insulin decreases isoflurane MAC in a dose-related manner independently of its effects on the blood concentration of glucose. The sites at which insulin acts to decrease MAC appear to be supraspinal rather than spinal. The effect may be due to a capacity of insulin to produce analgesia through an action on one or more neurotransmitter receptors.
  
  
  CONCLUSIONS
  Intrathecal and IV insulin administration equally decrease isoflurane MAC in rats, regardless of the concentration of blood sugar. These findings indicate that although insulin decreases MAC, the decrease is not mediated by actions on the spinal cord.
authors.affiliation: *Department of Anesthesia and Perioperative Care, University of California, San Francisco, California; and †Department of Anesthesia, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yilei
authors.initials: Y
authors.lastname: Xing
authors.forename: Jim
authors.initials: J
authors.lastname: Sonner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Laster
authors.forename: Wella
authors.initials: W
authors.lastname: Abaigar
authors.forename: Valerie B
authors.initials: VB
authors.lastname: Caraiscos
authors.forename: Beverley
authors.initials: B
authors.lastname: Orser
authors.forename: Edmond I
authors.initials: EI
authors.lastname: Eger
mesh_terms: D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D007328:Insulin / Q000493:pharmacokinetics*; D007530:Isoflurane / Q000493:pharmacokinetics*; D008297:Male; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018685:Anesthetics, Inhalation; D001786:Blood Glucose; D007328:Insulin; D007530:Isoflurane