Preoperative carbohydrate supplementation attenuates post-surgery insulin resistance via reduced inflammatory inhibition of the insulin-mediated restraint on muscle pyruvate dehydrogenase kinase 4 expression. Issue 6 (December 2015)

• Record Type: Journal Article
• Authors: Gjessing, Petter Fosse; Constantin-Teodosiu, Dumitru; Hagve, Martin; Lobo, Dileep N.; Revhaug, Arthur; Irtun, Øivind
• Is Part Of: Clinical nutrition. Volume 34:Issue 6(2015:Dec.)
• Page Start: 1177
• Page End: 1183
• Publication Date: 2015-12
• Subjects: Preoperative carbohydrate supplementation -- Postoperative insulin resistance -- Inflammation -- Insulin signaling -- Pyruvate dehydrogenase kinase 4; CHO carbohydrate -- FOXO1 forkhead transcription factor 1 -- IKKβ inhibitor κB kinase -- IL-6 interleukin 6 -- IRS1 insulin receptor substrate 1 -- JNK c-Jun N-terminal kinase -- PDC pyruvate dehydrogenase complex -- PDK4 pyruvate dehydrogenase kinase 4 -- SOCS3 suppressor of cytokine signaling 3 -- TNF-α tumor necrosis factor α; Critically ill -- Nutrition -- Periodicals; Diet therapy -- Periodicals; Parenteral feeding -- Periodicals; Enteral feeding -- Periodicals; Enteral Nutrition -- Periodicals; Parenteral Nutrition -- Periodicals; Metabolism -- Periodicals; Diétothérapie -- Périodiques; Alimentation parentérale -- Périodiques; Alimentation entérale -- Périodiques; Nutrition -- Périodiques; Diet therapy; Enteral feeding; Nutrition; Parenteral feeding; Electronic journals; Periodicals; Electronic journals; 615.854
• DOI: 10.1016/j.clnu.2014.12.004
• Languages: English
• ISSNs: 0261-5614

Abstract

Summary: 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.