title: Biophysical and pharmacological properties of glucagon-like peptide-1 in rats under isoflurane anesthesia.
abstract: BACKGROUND
  Glucagon-like peptide-1 (GLP-1) increases insulin secretion and has an important role in maintaining glucose homeostasis. In this study, we evaluated the biophysical and pharmacological properties of GLP-1 by performing in vivo and in vitro experiments to determine the applicability of GLP-1 in glycemic control in rats under isoflurane anesthesia.
  
  
  METHODS
  Levels of portal GLP-1, insulin, and glucose and dipeptidyl peptidase-4 activity were measured in the basal fasting state and after gastric glucose load before, during, and after exposure to 30% O(2) in air (control) or 1.4% isoflurane in a mixture of 30% O(2) and air. The direct effects of isoflurane on GLP-1 secretion were assessed in human enteroendocrine NCI-H716 cells. Insulin release from isolated pancreatic islets was measured using a radioimmunoassay. Single pancreatic β-cell membrane potentials were recorded using whole-cell current-clamp patches perforated by β-escin.
  
  
  RESULTS
  In fasting rats, inhalation of isoflurane led to a decrease in the basal levels of GLP-1 but did not affect insulin and glucose levels. Levels of GLP-1, insulin, and glucose increased after gastric administration of glucose in control rats. However, isoflurane attenuated the glucose-induced increase in GLP-1 and insulin levels and increased plasma glucose levels. In contrast, isoflurane did not affect dipeptidyl peptidase-4 activity before or after gastric glucose loading. Isoflurane (0.35 mM) inhibited GLP-1 release in NCI-H716 cells; this finding was similar to that observed in in vivo studies. In perifusion experiments, isoflurane (0.35 mM) inhibited glucose-induced insulin release, whereas exogenous GLP-1 (10 nM) enhanced insulin release. Importantly, combined administration of isoflurane and GLP-1 enhanced both phases of glucose-induced insulin release to an extent similar to that achieved with GLP-1 alone. Whole-cell patches showed that exposure to GLP-1 (10 nM) led to nearly complete restoration of glucose-stimulated depolarization that had been suppressed by isoflurane (0.35 mM).
  
  
  CONCLUSIONS
  GLP-1 secretion is impaired during isoflurane anesthesia. However, our study showed that the insulinotropic action of GLP-1 was not affected by isoflurane. Furthermore, exposure to GLP-1 increased the membrane activity of pancreatic β-cells, preventing isoflurane-induced impairment of glucose-induced insulin secretion. These results support the hypothesis that GLP-1-based therapy may be a useful approach for achieving intraoperative glycemic control.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan. takashika@kochi-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawano
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tanaka
authors.forename: Haidong
authors.initials: H
authors.lastname: Chi
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
authors.forename: Fumimoto
authors.initials: F
authors.lastname: Yamazaki
authors.forename: Sonoe
authors.initials: S
authors.lastname: Kitamura
authors.forename: Naoko
authors.initials: N
authors.lastname: Kumagai
authors.forename: Masataka
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects*; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D007530:Isoflurane; D018819:Dipeptidyl Peptidase 4