The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs.

Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine model of sepsis, we explored the across organ net fluxes of gluconeogenic substrates.

Statin treatment reduces leucine turnover, but does not affect endogenous production of beta-hydroxy-beta-methylbutyrate (HMB).

Background: Statins, or hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, are one of the most commonly prescribed medications for lowering cholesterol. Myopathic side-effects ranging from pain and soreness to critical rhabdomyolysis are commonly reported and often lead to discontinuation. The pathophysiological mechanism is, in general, ascribed to a downstream reduction of Coenzyme Q10 synthesis.

Postprandial concentration of circulating branched chain amino acids are able to predict the carbohydrate content of the ingested mixed meal.

Background: The amount of the macronutrients protein and carbohydrate (CHO) in a mixed meal is known to affect each other's digestion, absorption, and subsequent metabolism. While the effect of the amount of dietary protein and fat on the glycemic response is well studied, the ability of postprandial plasma amino acid patterns to predict the meal composition is unknown.

Objective: To study the postprandial plasma amino acid patterns in relation to the protein, CHO, and fat content of different mixed meals and to investigate if these patterns can predict the macronutrient meal composition.

Nutritional support for critically ill patients in the intensive care unit.

Patients in intensive care have increased nutritional needs but are often incapable of eating independently. When should intravenous parenteral nutrition be started, and what is the optimal dose? Here we review the recently updated European guidelines on nutritional support in intensive care patients.

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

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.

Skeletal muscle mitochondria exhibit decreased pyruvate oxidation capacity and increased ROS emission during surgery-induced acute insulin resistance.

Development of acute insulin resistance represents a negative factor after surgery, but the underlying mechanisms are not fully understood. We investigated the postoperative changes in insulin sensitivity, mitochondrial function, enzyme activities, and release of reactive oxygen species (ROS) in skeletal muscle and liver in pigs on the 2nd postoperative day after major abdominal surgery. Peripheral and hepatic insulin sensitivity were assessed by D-[6,6-²H₂]glucose infusion and hyperinsulinemic euglycemic step clamping.

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

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.

The acute phase of experimental cardiogenic shock is counteracted by microcirculatory and mitochondrial adaptations.

The mechanisms contributing to multiorgan dysfunction during cardiogenic shock are poorly understood. Our goal was to characterize the microcirculatory and mitochondrial responses following ≥ 10 hours of severe left ventricular failure and cardiogenic shock. We employed a closed-chest porcine model of cardiogenic shock induced by left coronary microembolization (n = 12) and a time-matched control group (n = 6).

Single-dose carbohydrate treatment in the immediate preoperative phase diminishes development of postoperative peripheral insulin resistance.

Background & Aims: Preoperative oral carbohydrate (CHO) treatment is known to reduce postoperative insulin resistance, but the necessity of a preoperative evening dose is uncertain. We investigated the effect of single-dose CHO treatment two hours before surgery on postoperative insulin sensitivity.

Methods: Thirty two pigs (∼ 30 kg) were randomized to 4 groups (n = 8) followed by D-[6,6-(2)H2] glucose infusion and hyperinsulinemic-euglycemic step clamping.

The Accu-Chek Mobile blood glucose monitoring system used under controlled conditions meets ISO 15197 standards in the hands of diabetes patients.

Background: Self-monitoring of blood glucose is a cornerstone of diabetes management. The aim of this study was to evaluate the analytical quality and the ease of use of the Accu-Chek Mobile, a new glucose monitoring system designed for capillary blood testing by diabetic patients.

Materials And Methods: The performance of the Accu-Chek Mobile was evaluated both in the hands of a scientist and of diabetes patients.

High intensity interval training alters substrate utilization and reduces oxygen consumption in the heart.

Aims: although exercise training induces hypertrophy with improved contractile function, the effect of exercise on myocardial substrate metabolism and cardiac efficiency is less clear. High intensity training has been shown to produce more profound effects on cardiovascular function and aerobic capacity than isocaloric low and moderate intensity training. The aim of the present study was to explore metabolic and mechanoenergetic changes in the heart following endurance exercise training of both high and moderate intensity.

Cardioprotective effect of the PPAR ligand tetradecylthioacetic acid in type 2 diabetic mice.

Tetradecylthioacetic acid (TTA) is a novel peroxisome proliferator-activated receptor (PPAR) ligand with marked hypolipidemic and insulin-sensitizing effects in obese models. TTA has recently been shown to attenuate dyslipidemia in patients with type 2 diabetes, corroborating the potential for TTA in antidiabetic therapy. In a recent study on normal mice, we showed that TTA increased myocardial fatty acid (FA) oxidation, which was associated with decreased cardiac efficiency and impaired postischemic functional recovery.

Heptanol triggers cardioprotection via mitochondrial mechanisms and mitochondrial potassium channel opening in rat hearts.

Aim: To investigate mechanisms behind heptanol (Hp)-induced infarct size reduction and in particular if protection by pre-treatment with Hp is triggered through mitochondrial mechanisms.

Methods: Langendorff perfused rat hearts, isolated mitochondria and isolated myocytes were used. Infarct size, mitochondrial respiration, time to mitochondrial permeability transition pore (MPTP) opening and AKT and glycogen synthase kinase 3 beta (GSK-3β) phosphorylation were examined.

Hyperinsulinemic euglycemic step clamping with tracer glucose infusion and labeled glucose infusate for assessment of acute insulin resistance in pigs.

The present study aimed to establish hyperinsulinemic euglycemic step clamping with tracer glucose infusion and labeled glucose infusate (step hot-GINF HEC) for assessment of acute insulin resistance in anesthetized pigs and to arrange for combination with invasive investigative methods. Tracer enrichment was measured during D-[6,6-(2)H(2)]glucose infusion before and after surgical instrumentation (n = 8). Insulin dose-response characteristics were determined by two step hot-GINF HEC procedures, with accordingly labeled glucose infusates performed at a total of six insulin infusion rates ranging from 0.

Cardiac peroxisome proliferator-activated receptor-alpha activation causes increased fatty acid oxidation, reducing efficiency and post-ischaemic functional loss.

Aims: Myocardial fatty acid (FA) oxidation is regulated acutely by the FA supply and chronically at the transcriptional level owing to FA activation of peroxisome proliferator-activated receptor-alpha (PPARalpha). However, in vivo administration of PPARalpha ligands has not been shown to increase cardiac FA oxidation. In this study we have examined the cardiac response to in vivo administration of tetradecylthioacetic acid (TTA, 0.