Cand.med. Martin Hagve disputerer for ph.d.-graden i helsevitenskap og vil offentlig forsvare avhandlingen:
“Postoperative insulin resistance – metabolic alterations and therapeutic approaches”
Kort sammendrag av avhandlingen:
After surgery, an acute state of insulin resistance arises, whose magnitude correlates with postoperative outcome and length of hospital stay. Postoperative insulin resistance in the immediate phase mainly arises in muscle, but the underlying cellular mechanisms of its development are largely unknown. Stress hormones and inflammation are thought to be initiating factors, which in turn may negatively impact the mitochondria, the main center for energy production in the cell and the most important source of so-called oxidative stress or reactive oxygen species (ROS). The present work was designed to investigate metabolic alterations with special focus on glucose utilization, hormonal changes, mitochondrial function and oxidative stress in response to surgical trauma, using a porcine model. We also tested two therapeutic approaches for improving postoperative insulin sensitivity – oral administration of a single-dose carbohydrate load prior to surgery, and a perioperative infusion of glucagon-like peptide 1 (GLP-1). Insulin sensitivity was evaluated by so-called glucose clamp technique. We observed reduced skeletal muscle insulin sensitivity, along with an immediate rise in cortisol levels and a subsequent increase in glucagon after surgery. Skeletal muscle mitochondria exhibited reduced respiration (with pyruvate) in the postoperative phase, while ROS levels in skeletal muscle and liver were increased. Finally, we found that a single oral carbohydrate load, as well as intraoperative infusion of GLP-1 could diminish/prevent postoperative insulin resistance.
(Avhandlingen er tilgjengelig for utlån hos Seksjon for utdanningstjenester frem til disputasdato)
Veiledere
Hovedveileder professor Øivind Irtun, Institutt for klinisk medisin, UiT Norges arktiske universitet
Biveileder professor Terje Larsen, Institutt for medisinsk biologi, UiT Norges arktiske universitet
Biveileder førsteamanuensis Petter Gjessing, Institutt for klinisk medisin, UiT Norges arktiske universitet
Bedømmelseskomiteen
Professor Labros Sidossis, Department of Kinesiology and Health, Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Jersey, USA – 1. opponent
Professor Egil Johnson, Avdeling for Gastro- og Barnekirurgi, Oslo Universitetssykehus – 2. opponent
Førsteamanuensis Marit Hansen, Bryst- og endokrinkirurgisk avdeling, Universitetssykehuset Nord Norge, UIT – Norges arktiske universitet – leder av komiteen
Disputasleder
Professor Tom Dønnem, Institutt for klinisk medisin, UiT - Norges arktiske universitet
Prøveforelesning over oppgitt emne holdes kl. 10.15, samme sted: “Is acute insulin resistance a negative or a positive factor after surgery? Discuss in terms of evolution and current day understanding of metabolic regulation”