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

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 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: Petter Fosse Gjessing, Dumitru Constantin-Teodosiu, Martin Hagve, Dileep N Lobo, Arthur Revhaug, Øivind Irtun
• Journal: Clinical nutrition (Edinburgh, Scotland) (Clin Nutr) Vol. 34 Issue 6 Pg. 1177-83 (Dec 2015) ISSN: 1532-1983 [Electronic] England
• PMID: 25534879 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Chemical References

• Blood Glucose
• Dietary Carbohydrates
• Forkhead Transcription Factors
• Insulin
• Insulin Receptor Substrate Proteins
• Protein Kinases
• pyruvate dehydrogenase kinase 4
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Blood Glucose (metabolism)
• Dietary Carbohydrates (administration & dosage)
• Dietary Supplements
• Digestive System Surgical Procedures
• Fasting
• Forkhead Transcription Factors (genetics, metabolism)
• Glucose Clamp Technique (veterinary)
• Hyperinsulinism (drug therapy, veterinary)
• Inflammation (drug therapy)
• Insulin (blood)
• Insulin Receptor Substrate Proteins (genetics, metabolism)
• Insulin Resistance
• Muscle, Skeletal (drug effects, metabolism)
• Postoperative Period
• Preoperative Care (veterinary)
• Protein Kinases (genetics, metabolism)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Single-Blind Method
• Swine