title: Preoperative carbohydrate supplementation attenuates post-surgery insulin resistance via reduced inflammatory inhibition of the insulin-mediated restraint on muscle pyruvate dehydrogenase kinase 4 expression.
abstract: OBJECTIVE
  We hypothesized that the so far poorly understood improvement in postoperative insulin sensitivity, when surgery is preceded by a carbohydrate (CHO) drink, occurs via attenuation of skeletal muscle inflammatory responses to surgery, improved insulin signaling and attenuated expression of muscle pyruvate dehydrogenase kinase (PDK) 4.
  
  
  METHODS
  Vastus lateralis muscle biopsies, collected before and after major abdominal surgery and during postoperative hyperinsulinaemic-euglycaemic clamping from 16 pigs randomized to either 200 ml of a CHO-supplemented drink 2 h before surgery (CHO, 25 g; n = 8), or preoperative overnight fasting (fasted; n = 8), were analyzed by fast qRT-PCR and IR-Western blotting.
  
  
  RESULTS
  During clamping, expression of IKKβ, SOCS3 and the ratio of phosphorylated/total JNK2 proteins were lower in the CHO group than in the fasted group (-1.0 vs. 2.9-fold, P < 0.001; -0.6 vs. 3.2-fold, P < 0.01; and -0.5 vs. 1.1-fold, P < 0.02, respectively). Furthermore, the ratio of Ser(307)-phosphorylated (inhibition)/total IRS1 protein was reduced only in the CHO group (-2.4 fold, P < 0.02), whereas FOXO1 phosphorylation (inactivation), which correlated negatively with PDK4 mRNA (r(2) = 0.275, P < 0.05), was lower in the CHO group than in the fasted group (-1.1-fold, P > 0.05 vs. -2.3-fold, P = 0.05). Post-surgery, PDK4 mRNA increased ∼20-fold (P < 0.01) in both groups, but was reversed to a greater extent by insulin in the CHO group (-40.5 vs. -22.7-fold, P < 0.05), resulting in 5-fold lower PDK4 protein levels, which correlated negatively with insulin-stimulated whole-body glucose disposal rates (r(2) = -0.265, P < 0.05).
  
  
  CONCLUSIONS
  Preoperative carbohydrate supplementation was found to ameliorate postoperative insulin sensitivity by reducing muscle inflammatory responses and improved insulin inhibition of FOXO1-mediated PDK4 mRNA and protein expression after surgery.
authors.affiliation: Department of Digestive Surgery, University Hospital of North Norway, Tromsø, Norway; Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. Electronic address: petter.fosse.gjessing@unn.no.
authors.forename: Petter Fosse
authors.initials: PF
authors.lastname: Gjessing
authors.affiliation: School of Life Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom.
authors.forename: Dumitru
authors.initials: D
authors.lastname: Constantin-Teodosiu
authors.affiliation: Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
authors.forename: Martin
authors.initials: M
authors.lastname: Hagve
authors.affiliation: Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, National Institute for Health Research Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical Centre, United Kingdom.
authors.forename: Dileep N
authors.initials: DN
authors.lastname: Lobo
authors.affiliation: Department of Digestive Surgery, University Hospital of North Norway, Tromsø, Norway; Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
authors.forename: Arthur
authors.initials: A
authors.lastname: Revhaug
authors.affiliation: Department of Digestive Surgery, University Hospital of North Norway, Tromsø, Norway; Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Irtun
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D019587:Dietary Supplements; D013505:Digestive System Surgical Procedures; D005215:Fasting; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015309:Glucose Clamp Technique / Q000662:veterinary; D006946:Hyperinsulinism / Q000188:drug therapy / Q000662:veterinary; D007249:Inflammation / Q000188:drug therapy; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D011184:Postoperative Period; D011300:Preoperative Care / Q000662:veterinary*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D016037:Single-Blind Method; D013552:Swine
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D051858:Forkhead Transcription Factors; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D051057:Proto-Oncogene Proteins c-akt
keywords: Inflammation; Insulin signaling; Postoperative insulin resistance; Preoperative carbohydrate supplementation; Pyruvate dehydrogenase kinase 4