Perioperative Infusion of Glucagon-Like Peptide-1 Prevents Insulin Resistance After Surgical Trauma in Female Pigs

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.

From gut microbiota to host appetite: gut microbiota-derived metabolites as key regulators

“…GLP-1 and PYY, two anorexigenic hormones [48,[78][79][80][81][82], can cross the BBB and act as direct brain neuropeptides to activate POMC [49,83]. In addition, GLP-1 and PYY help to increase insulin sensitivity and slow gastric emptying and intestinal motility to affect appetite [84][85][86][87]. Intriguingly, acute colonic propionate delivery decreases food intake and stimulates the secretion of PYY and GLP-1, while long-term colonic propionate delivery has little effects on PYY and GLP-1 release in humans [74], which may be associated with propionate resistance.…”

The Implication of Short-Chain Fatty Acids in Obesity and Diabetes

“… 53 , 78 , 80 While SCFA-dependent GPR43 signaling has been suggested to mediate host insulin sensitivity secretion by promoting glucagon-like peptide-1 (GLP-1) ( Figure 4A ). 19 , 81 , 82 Pingitore et al 83 show that insulin secretion is dependent on GPR43 and it is stimulated by acetate and propionate via the phospholipase C/protein kinase C pathway.…”

Type 2 Diabetes Complicated With Heart Failure: Research on Therapeutic Mechanism and Potential Drug Development Based on Insulin Signaling Pathway

“…And liraglutide can also reduce the NF-KB activation, thus reducing inflammatory cytokines ( Li et al, 2018 ). Importantly, GLP-1 may improve insulin sensitivity, glycemic control, and endothelial function, increase muscle microvascular perfusion, and stimulate angiogenesis, and these effects are retained in IR ( Hagve et al, 2019 ; Love et al, 2020 ).…”

“…At present, GLP-1 agonists have been used for the treatment of chronic IR. They have beneficial cardiovascular effects for T2DM patients and are very suitable for T2DM patients with cardiomyopathy ( Hagve et al, 2019 ; Love et al, 2020 ). Intervention of GLP-1 RA to CRTd therapy in diabetic patients significantly improved LVEF and the 6 min walking test, reduced the arrhythmic burden, and reduced hospital admissions for heart failure worsening by increasing the CRTd responder rate ( Sardu et al, 2018 ).…”