PMID- 25534879 OWN - NLM STAT- MEDLINE DCOM- 20160929 LR - 20220330 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 34 IP - 6 DP - 2015 Dec TI - Preoperative carbohydrate supplementation attenuates post-surgery insulin resistance via reduced inflammatory inhibition of the insulin-mediated restraint on muscle pyruvate dehydrogenase kinase 4 expression. PG - 1177-83 LID - S0261-5614(14)00302-1 [pii] LID - 10.1016/j.clnu.2014.12.004 [doi] AB - BACKGROUND & AIMS: 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 IKKbeta, 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 approximately 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. CI - Copyright (c) 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. FAU - Gjessing, Petter Fosse AU - Gjessing PF AD - Department of Digestive Surgery, University Hospital of North Norway, Tromso, Norway; Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromso, Tromso, Norway. Electronic address: petter.fosse.gjessing@unn.no. FAU - Constantin-Teodosiu, Dumitru AU - Constantin-Teodosiu D AD - School of Life Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom. FAU - Hagve, Martin AU - Hagve M AD - Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromso, Tromso, Norway. FAU - Lobo, Dileep N AU - Lobo DN AD - 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. FAU - Revhaug, Arthur AU - Revhaug A AD - Department of Digestive Surgery, University Hospital of North Norway, Tromso, Norway; Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromso, Tromso, Norway. FAU - Irtun, Oivind AU - Irtun O AD - Department of Digestive Surgery, University Hospital of North Norway, Tromso, Norway; Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromso, Tromso, Norway. LA - eng GR - MR/K00414X/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20141211 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 0 (Blood Glucose) RN - 0 (Dietary Carbohydrates) RN - 0 (Forkhead Transcription Factors) RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.- (pyruvate dehydrogenase kinase 4) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Blood Glucose/metabolism MH - Dietary Carbohydrates/*administration & dosage MH - *Dietary Supplements MH - Digestive System Surgical Procedures MH - Fasting MH - Forkhead Transcription Factors/genetics/metabolism MH - Glucose Clamp Technique/veterinary MH - Hyperinsulinism/drug therapy/veterinary MH - Inflammation/drug therapy MH - Insulin/blood MH - Insulin Receptor Substrate Proteins/genetics/metabolism MH - *Insulin Resistance MH - Muscle, Skeletal/*drug effects/metabolism MH - Postoperative Period MH - Preoperative Care/*veterinary MH - Protein Kinases/genetics/*metabolism MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - Single-Blind Method MH - Swine OTO - NOTNLM OT - Inflammation OT - Insulin signaling OT - Postoperative insulin resistance OT - Preoperative carbohydrate supplementation OT - Pyruvate dehydrogenase kinase 4 EDAT- 2014/12/24 06:00 MHDA- 2016/09/30 06:00 CRDT- 2014/12/24 06:00 PHST- 2014/08/01 00:00 [received] PHST- 2014/11/25 00:00 [revised] PHST- 2014/12/04 00:00 [accepted] PHST- 2014/12/24 06:00 [entrez] PHST- 2014/12/24 06:00 [pubmed] PHST- 2016/09/30 06:00 [medline] AID - S0261-5614(14)00302-1 [pii] AID - 10.1016/j.clnu.2014.12.004 [doi] PST - ppublish SO - Clin Nutr. 2015 Dec;34(6):1177-83. doi: 10.1016/j.clnu.2014.12.004. Epub 2014 Dec 11.