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Perioperative infusion of glucagon-like peptide-1 prevents insulin resistance after surgical trauma in female pigs

Hagve, Martin Iversen; Gjessing, Petter Fosse; Hole, Mikal Jacob; Jansen, Kirsten M; Fuskevåg, Ole Martin; Mollnes, Tom Eirik; Larsen, Terje S; Irtun, Øivind
Journal article, Peer reviewed
Accepted version
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URI
http://hdl.handle.net/11250/2642110
Date
2019
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  • Institutt for klinisk og molekylær medisin [2070]
  • Publikasjoner fra CRIStin - NTNU [20955]
Original version
Endocrinology. 2019, 160 (12), 2892-2902.   10.1210/en.2019-00374
Abstract
Insulin resistance is an independent negative predictor of outcome after elective surgery and increases mortality among surgical patients in intensive care. The incretin hormone glucagon-like peptide-1 (GLP-1) potentiates glucose-induced insulin release from the pancreas but may also increase insulin sensitivity in skeletal muscle and directly suppress hepatic glucose release. Here, we investigated whether a perioperative infusion of GLP-1 could counteract the development of insulin resistance after surgery. Pigs were randomly assigned to three groups; surgery/control, surgery/GLP-1, and sham/GLP-1. Both surgery groups underwent major abdominal surgery. Whole-body glucose disposal (WGD) and endogenous glucose release (EGR) were assessed preoperatively and postoperatively using D-[6,6-2H2]-glucose infusion in combination with hyperinsulinemic euglycemic step-clamping. In the surgery/control group, peripheral insulin sensitivity (i.e., WGD) was reduced by 44% relative to preoperative conditions, whereas the corresponding decline was only 9% for surgery/GLP-1 (P < 0.05). Hepatic insulin sensitivity (i.e., EGR) remained unchanged in the surgery/control group but was enhanced after GLP-1 infusion in both surgery and sham animals (40% and 104%, respectively, both P < 0.05). Intraoperative plasma glucose increased in surgery/control (∼20%) but remained unchanged in both groups receiving GLP-1 (P < 0.05). GLP-1 diminished an increase in postoperative glucagon levels but did not affect skeletal muscle glycogen or insulin signaling proteins after surgery. We show that GLP-1 improves intraoperative glycemic control, diminishes peripheral insulin resistance after surgery, and suppresses EGR. This study supports the use of GLP-1 to prevent development of postoperative insulin resistance.
Publisher
Oxford University Press (OUP)
Journal
Endocrinology

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