Preoperative carbohydrate supplementation attenuates post-surgery insulin resistance via reduced inflammatory inhibition of the insulin-mediated restraint on muscle pyruvate dehydrogenase kinase 4 expression

Clin Nutr. 2015 Dec;34(6):1177-83. doi: 10.1016/j.clnu.2014.12.004. Epub 2014 Dec 11.

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.

Keywords: Inflammation; Insulin signaling; Postoperative insulin resistance; Preoperative carbohydrate supplementation; Pyruvate dehydrogenase kinase 4.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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