术前补充碳水化合物减轻术后胰岛素抵抗（通过减少胰岛素对肌肉丙酮酸脱氢酶激酶4表达的炎性抑制）

Clin Nutr. 2015 Dec;34(6):1177-83.

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

Gjessing PF, Constantin-Teodosiu D, Hagve M, Lobo DN, Revhaug A, Irtun Ø.

University Hospital of North Norway, Tromsø, Norway.

Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.

School of Life Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, United Kingdom.

Nottingham Digestive Diseases Centre, National Institute for Health Research Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical Centre, United Kingdom.

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

PMID: 25534879

DOI: 10.1016/j.clnu.2014.12.004