Changes in insulin action and GLUT-4 with 6 days of inactivity in endurance runners

1996 ◽  
Vol 80 (1) ◽  
pp. 240-244 ◽  
Author(s):  
M. D. Vukovich ◽  
P. J. Arciero ◽  
W. M. Kohrt ◽  
S. B. Racette ◽  
P. A. Hansen ◽  
...  
Keyword(s):  
Infusion Rate ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Glucose Disposal ◽  
Inactive State ◽  
Transporter Protein ◽  
Glut 4 ◽  
Insulin Infusion Rate ◽  
Endurance Runners ◽  
Trained Runners

The purpose of this investigation was to determine whether decreased insulin action after 6 days of inactivity in endurance-trained runners was associated with a decrease in skeletal muscle glucose transporter protein levels (GLUT-4) in the gastrocnemius muscle. Seven endurance runners (5 men and 2 women) volunteered to participate in this investigation. All subjects had normal glucose tolerance as determined by the National Diabetes Data Group guidelines. Each individual completed two hyperinsulinemic euglycemic clamps at insulin infusion rates of 15 (LO) and 40 (HI) mU.m-2.min-1, one approximately 18 h after a training bout and the second after 6 days of inactivity (IA). Muscle biopsies for the measurement of GLUT-4 were obtained from the gastrocnemius before each clamp. Glucose disposal rates during the last 30 min of each insulin infusion were significantly reduced after 6 days of IA, averaging 6.45 +/- 1.04 mg.kg fat-free mass (FFM)-1.min-1 before and 4.55 +/- 0.56 mg.kg FFM-1.min-1 after detraining for the LO insulin infusion rate and 13.77 +/- 0.88 mg.kg FFM-1.min-1 before and 11.81 +/- 0.60 mg.kg FFM-1.min-1 after detraining for the HI insulin infusion rate (both P < 0.05), despite the fact that plasma insulin was higher in the inactive state (LO, 19.2 +/- 0.9 microU/ml before and 23.4 +/- 1.5 microU/ml after detraining; HI, 56.0 +/- 2.0 microU/ml before and 61.6 +/- 1.6 microU/ml after detraining; P < 0.05)). Calculated insulin clearance was greater in the trained than in the inactive state (P < 0.03). Muscle GLUT-4 transporter protein after 6 days of IA was reduced by 17.5 +/- 5.4% (P < 0.02). These results demonstrate that 6 days of IA reduces insulin action in endurance-trained runners and suggest that a reduction in muscle GLUT-4 transporter level plays a role in the decrease in glucose disposal rates.

Hepatic and Peripheral Insulin Action in Chronic Renal Failure before and during Continuous Ambulatory Peritoneal Dialysis

1989 ◽  
Vol 77 (4) ◽  
pp. 383-388 ◽  
Author(s):  
A. Heaton ◽  
R. Taylor ◽  
D. G. Johnston ◽  
M. K. Ward ◽  
R. Wilkinson ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Infusion Rate ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Glucose Turnover ◽  
Insulin Infusion Rate ◽  
Hepatic Glucose ◽  
Total Glucose ◽  
Glucose Output

1. A three-step hyperinsulinaemic euglycaemic clamp was performed in six uraemic patients before dialysis and after 3 months of treatment with continuous ambulatory peritoneal dialysis, and in seven matched normal control subjects. Glucose turnover was assessed basally and during the clamp using [3-3H]glucose as a tracer. 2. The glucose infusion rate required to maintain euglycaemia was insignificantly higher in normal subjects compared with undialysed uraemic subjects at each insulin infusion rate. 3. The isotopically assessed total glucose turnover was also similar in normal and uraemic subjects. Basal hepatic glucose output was again similar in uraemic and control subjects and output was suppressed to a similar degree at each insulin infusion rate. 4. After treatment with continuous ambulatory peritoneal dialysis, the glucose infusion rate and the total glucose turnover during the clamp rose significantly at all three insulin concentrations (P < 0.05), but remained insignificantly different from normal control values. Hepatic glucose output was unchanged. 5. Peripheral insulin action was improved during continuous ambulatory peritoneal dialysis, but hepatic insulin action was unchanged.

Energy expenditure and substrate metabolism in ethanol-induced liver cirrhosis

1991 ◽  
Vol 260 (3) ◽  
pp. E338-E344 ◽  
Author(s):  
M. J. Muller ◽  
A. Fenk ◽  
H. U. Lautz ◽  
O. Selberg ◽  
H. Canzler ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Energy Expenditure ◽  
Metabolic Rate ◽  
Oxidation Rate ◽  
Infusion Rate ◽  
Glucose Oxidation ◽  
Insulin Infusion ◽  
Resting Metabolic Rate ◽  
Insulin Infusion Rate ◽  
Glucose Storage

Energy expenditure and substrate metabolism were investigated in 10 patients with alcoholic liver cirrhosis (EtOH-Ci) and 10 healthy controls (C). Resting metabolic rate (RMR) varied from 1,269 to 2,467 kcal/day in C and from 1,228 to 2,098 kcal/day in EtOH-Ci. RMR was significantly related to fat-free mass (FFM) in both groups, but EtOH-Ci decreased FFM and increased RMR when expressed per kilogram FFM (+33%). Glucose intolerance, hyperinsulinemia, and a decreased C-peptide-to-insulin ratio were observed in EtOH-Ci after a test meal. Concomitantly, nonoxidative glucose metabolism was reduced in association with normal increases in glucose oxidation. EtOH-Ci reduced insulin sensitivity (-59%) and maximal insulin-dependent glucose disposal (-40%) during a sequential two-step glucose clamp protocol (phase 1: 1 mU.kg body wt-1.min-1 insulin infusion rate + euglycemia; phase 2: 4 mU.kg body wt-1.min-1 insulin infusion rate + 165 mg/dl plasma glucose concentration). This was explained by reduced glucose storage (-99%, -51%) in association with normal responses in glucose oxidation rate, plasma lactate concentration, lipid oxidation rate, and rate of lipogenesis. Defective glucose storage was independent of reduced FFM. EtOH-Ci increased glucose-induced thermogenesis by 57%. We conclude that increased resting metabolic rate, enhanced thermogenesis, defective glucose storage, and normal glucose oxidation together result in increased energy needs and favor negative energy balance in patients with alcoholic cirrhosis.

Higher insulin infusion rate but not 24-h insulin consumption is associated with hypoglycemia in critically ill patients

2015 ◽  
Vol 110 (3) ◽  
pp. 322-327
Author(s):  
John J. Radosevich ◽  
Asad E. Patanwala ◽  
Paul D. Frey ◽  
Yong G. Lee ◽  
Holly Paddock ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Infusion Rate ◽  
Insulin Infusion ◽  
Insulin Infusion Rate

scholarly journals Short-term topiramate treatment does not improve insulin sensitivity or secretion in obese insulin-resistant women

2012 ◽  
Vol 167 (6) ◽  
pp. 839-845 ◽  
Author(s):  
Maria A Sleddering ◽  
Marieke Snel ◽  
Trea C M Streefland ◽  
Hanno Pijl ◽  
Ingrid M Jazet
Keyword(s):  
Insulin Sensitivity ◽  
Infusion Rate ◽  
Insulin Infusion ◽  
Cell Function ◽  
Controlled Study ◽  
Β Cell ◽  
Insulin Resistant ◽  
Insulin Infusion Rate ◽  
Long Term Treatment ◽  
Β Cell Function

ObjectiveLong-term treatment with topiramate reduces body weight and improves insulin sensitivity in obese humans. Our aim was to evaluate the effect of topiramate treatment for 4 weeks on insulin sensitivity and secretion, independent of weight loss.DesignRandomized, double-blind, crossover, placebo-controlled study.MethodsThirteen obese (BMI 36.6±1.3 kg/m2 (mean±s.e.m.)), insulin-resistant (homeostasis model of assessment-insulin resistance 2.0±0.2) women received topiramate (T, maximum dose of 75 mg) and placebo (P) for 4 weeks, separated by a 4-week washout period. Insulin sensitivity and β-cell function were assessed using a two-step hyperinsulinemic euglycemic clamp with stable isotopes and a hyperglycemic clamp.ResultsHepatic and peripheral insulin sensitivities were not affected by topiramate treatment (glucose disposal rate (step 1 (insulin infusion rate 10 mU/m2 per min) T: 17.5±0.8 vs P: 18.5±1.0 μmol/kgLBM per min, t=1.016, P=0.33; step 2 (insulin infusion rate 40 mU/m2 per min) T: 27.9±3.2 vs P: 28.8±1.9 μmol/kgLBM per min, t=0.418, P=0.68)). Subjects lost a small amount of weight during the topiramate period (T: −1.0±0.2 vs P: −0.1±0.2 kg, t=2842, P=0.15). There were no changes in body fat mass, blood pressure, and fasting glucose. β-Cell function was not affected by topiramate as evidenced by an unaltered area under the curve of early (0–10 min; T: 1929.6±265.7 vs P: 2024.7±333.6 pmol/l, t=−0.357, P=0.73) and late (80–120 min; T: 28 017.7±5029.9 vs P: 31 567.7±5376.2 pmol/l, t=−1.481, P=0.16) phase insulin levels during hyperglycemia. The use of topiramate was associated with significant side effects such as paresthesia, nausea, dizziness, and concentration problems.ConclusionsLow-dose topiramate treatment for 4 weeks, relative to placebo, had no significant effect on insulin sensitivity in overweight/obese adult females without established diabetes.

Alterations in liver, muscle, and adipose tissue insulin sensitivity in men with HIV infection and dyslipidemia

2006 ◽  
Vol 290 (1) ◽  
pp. E47-E53 ◽  
Author(s):  
D. N. Reeds ◽  
K. E. Yarasheski ◽  
L. Fontana ◽  
W. T. Cade ◽  
E. Laciny ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hiv Infection ◽  
Insulin Action ◽  
Plasma Insulin ◽  
Insulin Infusion ◽  
Glucose Production ◽  
Glucose Disposal ◽  
High Dose ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Stimulation Of

Dyslipidemia is common in patients with HIV infection. In this study, a two-stage euglycemic hyperinsulinemic clamp, with infusion of stable isotopically labeled tracers, was used to evaluate insulin action in skeletal muscle, liver, and adipose tissue in HIV-infected men with dyslipidemia (HIV-DL; plasma triglyceride >250 mg/dl and HDL <45mg/dl; n = 12), HIV-infected men without dyslipidemia (HIV w/o DL; n = 12), and healthy men ( n = 6). Basal rates of glucose production (glucose Ra), glucose disposal (glucose Rd), and lipolysis (palmitate Ra) were similar between groups. The relative suppression of glucose Ra(63 ± 4, 77 ± 2, and 78 ± 3%, P = 0.008) and palmitate Ra(49 ± 4, 63 ± 3, and 68 ± 3%, P = 0.005) during low-dose insulin infusion (plasma insulin ∼30 μU/ml), and the relative stimulation of glucose Rd(214 ± 21, 390 ± 25, and 393 ± 46%, P = 0.001) during high-dose insulin infusion (plasma insulin ∼75 μU/ml) were lower in HIV-DL than in HIV w/o DL and healthy volunteers, respectively. Suppression of basal glucose Racorrelated with plasma adiponectin ( r = 0.44, P = 0.02) and inversely with plasma IL-6 ( r = −0.49, P < 0.001). Stimulation of glucose Rdcorrelated directly with adiponectin ( r = 0.48, P < 0.01) and inversely with IL-6 ( r = −0.49, P = 0.02). We conclude that dyslipidemia in HIV-infected men is indicative of multiorgan insulin resistance, and circulating adipokines may be important in the pathogenesis of impaired insulin action.

scholarly journals Explorative Study of Pharmacokinetics and Pharmacodynamics after Change in Basal Insulin Infusion Rate

2011 ◽  
Vol 5 (1) ◽  
pp. 120-128 ◽  
Author(s):  
Charlotte A. Ihlo ◽  
Torsten Lauritzen ◽  
Jeppe Sturis ◽  
Ole Skyggebjerg ◽  
Jens S. Christiansen ◽  
...  
Keyword(s):  
Basal Insulin ◽  
Infusion Rate ◽  
Insulin Infusion ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Explorative Study ◽  
Insulin Infusion Rate

scholarly journals Metaheuristic Optimization of Insulin Infusion Protocols Using Historical Data with Validation Using a Patient Simulator

2020 ◽  
pp. 1-28
Author(s):  
Hongyu Wang ◽  
Lynne Chepulis ◽  
Ryan G. Paul ◽  
Michael Mayo
Keyword(s):  
Infusion Rate ◽  
Insulin Infusion ◽  
Search Algorithms ◽  
Health Board ◽  
District Health ◽  
Patient Simulator ◽  
Intravenous Insulin ◽  
Insulin Infusion Rate ◽  
Starting Point ◽  
Metaheuristic Search

Metaheuristic search algorithms are used to develop new protocols for optimal intravenous insulin infusion rate recommendations in scenarios involving hospital in-patients with Type 1 Diabetes. Two metaheuristic search algorithms are used, namely, Particle Swarm Optimization and Covariance Matrix Adaption Evolution Strategy. The Glucose Regulation for Intensive Care Patients (GRIP) serves as the starting point of the optimization process. We base our experiments on a methodology in the literature to evaluate the favorability of insulin protocols, with a dataset of blood glucose level/insulin infusion rate time series records from 16 patients obtained from the Waikato District Health Board. New and significantly better insulin infusion strategies than GRIP are discovered from the data through metaheuristic search. The newly discovered strategies are further validated and show good performance against various competitive benchmarks using a virtual patient simulator.

Adjustment of basal insulin infusion rate in T1DM by hybrid PSO

2014 ◽  
Vol 19 (7) ◽  
pp. 1921-1937 ◽  
Author(s):  
Zhijiang Lou ◽  
Bo Liu ◽  
Hongzhi Xie ◽  
Youqing Wang
Keyword(s):  
Basal Insulin ◽  
Infusion Rate ◽  
Insulin Infusion ◽  
Insulin Infusion Rate

scholarly journals Oxyntomodulin ameliorates glucose intolerance in mice fed a high-fat diet

2008 ◽  
Vol 294 (1) ◽  
pp. E142-E147 ◽  
Author(s):  
Edwin T. Parlevliet ◽  
Annemieke C. Heijboer ◽  
Janny P. Schröder-van der Elst ◽  
Louis M. Havekes ◽  
Johannes A. Romijn ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Insulin Action ◽  
Insulin Infusion ◽  
Glucose Production ◽  
Tolerance Test ◽  
Glucose Disposal ◽  
Insulin Levels ◽  
Insulin Resistant

We evaluated the acute effects of OXM on glucose metabolism in diet-induced insulin-resistant male C57Bl/6 mice. To determine the effects on glucose tolerance, mice were intraperitoneally injected with OXM (0.75, 2.5, or 7.5 nmol) or vehicle prior to an ip glucose tolerance test. OXM (0.75 nmol/h) or vehicle was infused during a hyperinsulinemic euglycemic clamp to quantify insulin action on glucose production and disposal. OXM dose-dependently improved glucose tolerance as estimated by AUC for glucose (OXM: 7.5 nmol, 1,564 ± 460, P < 0.01; 2.5 nmol, 1,828 ± 684, P < 0.01; 0.75 nmol, 2,322 ± 303, P < 0.05; control: 2,790 ± 222 mmol·l−1·120 min). Insulin levels in response to glucose administration were higher in 7.5 nmol OXM-treated animals compared with controls. In basal clamp conditions, OXM increased EGP (82.2 ± 14.7 vs. 39.9 ± 5.7 μmol·min−1·kg−1, P < 0.001). During insulin infusion, insulin levels were twice as high in OXM-treated mice compared with controls (10.6 ± 2.8 vs. 4.4 ± 2.2 ng/ml, P < 0.01). Consequently, glucose infusion rate (118.6 ± 30.8 vs. 38.8 ± 26.4 μl/h, P < 0.001) and glucose disposal (88.1 ± 13.0 vs. 45.2 ± 6.9 μmol·min−1·kg−1, P < 0.001) were enhanced in mice that received OXM. In addition, glucose production was more suppressed during OXM infusion (35.7 ± 15.5 vs. 15.8 ± 11.4% inhibition, P < 0.05). However, if these data were expressed per unit concentration of circulating insulin, OXM did not affect insulin action on glucose disposal and production. These results indicate that OXM beneficially affects glucose metabolism in diet-induced insulin-resistant C57Bl/6 mice. It ameliorates glucose intolerance, most likely because it elevates glucose-induced plasma insulin concentrations. OXM does not appear to impact on insulin action.

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