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

Gjessing, Petter Fosse; Fuskevåg, Ole-Martin; Hagve, Martin; Revhaug, Arthur; Irtun, Øivind

doi:10.1152/ajpendo.00701.2009

Cited by 10 publications

(12 citation statements)

References 26 publications

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“…This correlates with the findings of Gjessing et al. [28] who showed that basal‐ and insulin‐stimulated glucose utilization was twice as high in pigs compared to human beings. The group also demonstrated moderate peripheral and hepatic insulin unresponsiveness as a result of surgical trauma [28].…”

Section: Discussionsupporting

confidence: 91%

“…[28] who showed that basal‐ and insulin‐stimulated glucose utilization was twice as high in pigs compared to human beings. The group also demonstrated moderate peripheral and hepatic insulin unresponsiveness as a result of surgical trauma [28]. In this respect, the use of a percutaneous model in our study with avoidance of trauma is important.…”

Section: Discussionmentioning

confidence: 99%

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Percutaneous Catheter-based Intracoronary Infusion of Insulin - A Dose Finding Study in the Porcine Model

Slettom

Jonassen

Tuseth

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

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Insulin given at immediate reperfusion reduces myocardial infarct size in the in vitro and the ex vivo rat heart. In vivo, insulin may cause hypoglycaemia, hypokalaemia and elevation of catecholamines, potentially harmful during an acute myocardial infarction. The purpose of this study was to evaluate tolerance and safety of intracoronary insulin infusions in a porcine model applying percutaneous intervention techniques.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Percutaneous Catheter-based Intracoronary Infusion of Insulin - A Dose Finding Study in the Porcine Model

Slettom

Jonassen

Tuseth

et al. 2011

Basic &Amp; Clinical Pharmacology &Amp; Toxicology

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“…The experimental protocol with 5 consecutive HECs by progressively increasing insulin infusion rates allows differentiation between impaired peripheral insulin sensitivity and response. 17,18 Because dexamethasone treatment affected ISI significantly only during HEC-I and HEC-II, we propose that the observed peripheral insulin resistance is predominately characterized by decreased insulin sensitivity and less by decreased insulin response (assessed as SSGIR and ISI during the highest insulin infusion rate during HEC-IV and HEC-V).…”

Section: Discussionmentioning

confidence: 97%

Effects of Dexamethasone‐21‐Isonicotinate on Peripheral Insulin Action in Dairy Cows 5 days after Surgical Correction of Abomasal Displacement

Kusenda

Kaske

Marion

et al. 2012

Veterinary Internal Medicne

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Background: Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood.Hypothesis: Dexamethasone treatment affects whole body insulin sensitivity. Animals: Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement.Methods: Randomized, blinded, case-control study. Treatment with dexamethasone-21-isonicotinate (DG; 40 lg/kg IM; n = 6) or saline (control group [CG], 15 mL IM, n = 6) on day 0 (d0). Blood samples were obtained before (d0) and after treatment (d1 and d2), and analyzed for glucose, insulin, and nonesterified fatty acid (NEFA) concentrations. Hepatic triglycerides (TAG) were measured in liver samples taken on d0 and d2. Five consecutive hyperinsulinemic-euglycemic clamps (HEC-I-V; insulin dosages: 0.1, 0.5, 2, 5, 10 mU/kg/min, respectively) were performed on d1 and steady state glucose infusion rate (SSGIR), insulin concentration (SSIC), insulin sensitivity index (ISI = SSGIR/SSIC), and plasma NEFA concentration (SSNEFA) were assessed.Results: Compared with CG-cows, DG-cows on d1 had higher plasma glucose (P = .004) and insulin (P < .001) concentrations, decreased SSGIR (HEC-II, P = .002; HEC-IV, P = .033), ISI (HEC-I, P < .015; HEC-II, P = .004), and insulin-stimulated decrease in SSNEFA (HEC-II, P = .006; HEC-III, P = .01; HEC-IV, P = .003; HEC-V, P = .011). Decrease in hepatic TAG content in DG-cows was higher compared with CG-cows (P < .001).Conclusions and Clinical Importance: Dexamethasone decreases whole body insulin sensitivity and affects glucose and lipid metabolism in early lactating dairy cows.

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“…Basal glucose turnover was assessed during the last 30 min of a 90-min-long primed (6 mg/kg) continuous (0.12 mg·kg Ϫ1 ·min Ϫ1 ) infusion of D- [6,6-2 H2]glucose (basal period), followed by peripheral and hepatic insulin sensitivity measurements consisting of two consecutive 120-min-long hyperinsulinemic (ϳ15 and 40 IU/ml) euglycemic (ϳ4.5 mmol/l) clamps with labeled glucose infusate (2.1 atom %enrichment). Insulin was infused at rates of 0.4 (low-insulin clamp) and 1.2 mU·kg Ϫ1 ·min Ϫ1 (high-insulin clamp) to differentiate between hepatic and peripheral insulin sensitivity, as described previously (20).…”

Section: Animalsmentioning

confidence: 99%

“…Determination of tracer enrichment in arterial blood measured by LC-MS/MS and calculations of endogenous glucose release and whole body glucose disposal were performed based on modified versions of Steele's equations (18,51), as described previously (20).…”

Section: Animalsmentioning

confidence: 99%

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

Hagve

Gjessing

Fuskevåg

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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Hagve M, Gjessing PF, Fuskevåg OM, Larsen TS, Irtun Ø. Skeletal muscle mitochondria exhibit decreased pyruvate oxidation capacity and increased ROS emission during surgery-induced acute insulin resistance. Am J Physiol Endocrinol Metab 308: E613-E620, 2015. First published February 10, 2015; doi:10.1152/ajpendo.00459.2014.-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-[6,6-2 H2]glucose infusion and hyperinsulinemic euglycemic step clamping. Surgical trauma elicited a decline in peripheral insulin sensitivity (ϳ34%, P Ͻ 0.01), whereas hepatic insulin sensitivity remained unchanged. Intramyofibrillar (IFM) and subsarcolemma mitochondria (SSM) isolated from skeletal muscle showed a postoperative decline in ADP-stimulated respiration (VADP) for pyruvate (ϳ61%, P Ͻ 0.05, and ϳ40%, P Ͻ 0.001, respectively), whereas VADP for glutamate and palmitoyl-Lcarnitine (PC) was unchanged. Mitochondrial leak respiration with PC was increased in SSM (1.9-fold, P Ͻ 0.05) and IFM (2.5-fold, P Ͻ 0.05), indicating FFA-induced uncoupling. The activity of the pyruvate dehydrogenase complex (PDC) was reduced (ϳ32%, P Ͻ 0.01) and positively correlated to the decline in peripheral insulin sensitivity (r ϭ 0.748, P Ͻ 0.05). All other mitochondrial enzyme activities were unchanged. No changes in mitochondrial function in liver were observed. Mitochondrial H2O2 and O2 ·Ϫ emission was measured spectrofluorometrically, and H2O2 was increased in SSM, IFM, and liver mitochondria (ϳ2.3-, ϳ2.5-, and ϳ2.3-fold, respectively, all P Ͻ 0.05). We conclude that an impairment in skeletal muscle mitochondrial PDC activity and pyruvate oxidation capacity arises in the postoperative phase along with increased ROS emission, suggesting a link between mitochondrial function and development of acute postoperative insulin resistance.reactive oxygen species; surgery; insulin resistance; mitochondria; skeletal muscle; liver AFTER SURGERY, the development of an acute transitory state of insulin resistance has been identified as a negative factor associated with increased morbidity and hospital stay (45), but the physiological and molecular mechanisms underlying this condition are not fully elucidated. The decline in insulin sensitivity in the postoperative phase has been thoroughly documented and is reflected mainly by impaired glucose disposal in peripheral tissues, primarily skeletal muscle (21, 36).Oxidative glucose disposal in skeletal muscle is regulated by the pyruvate dehydrogenase complex (PDC), which is an enzyme complex that regulates the flux of glucose-borne pyruvate into the mitochondria by converting pyruvate to acetylCoA, which subsequently enters the ...

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

Abstract: Gjessing PF, Fuskevåg O, Hagve M, Revhaug A, Irtun Ø. Hyperinsulinemic euglycemic step clamping with tracer glucose infusion and labeled glucose infusate for assessment of acute insulin resistance in pigs.

Cited by 10 publications

References 26 publications

Percutaneous Catheter-based Intracoronary Infusion of Insulin - A Dose Finding Study in the Porcine Model

Percutaneous Catheter-based Intracoronary Infusion of Insulin - A Dose Finding Study in the Porcine Model

Effects of Dexamethasone‐21‐Isonicotinate on Peripheral Insulin Action in Dairy Cows 5 days after Surgical Correction of Abomasal Displacement

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

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