Glucose production during exercise in humans: a-hv balance and isotopic-tracer measurements compared

1999 ◽  
Vol 87 (1) ◽  
pp. 111-115 ◽  
Author(s):  
R. Bergeron ◽  
M. Kjaer ◽  
L. Simonsen ◽  
J. Bülow ◽  
H. Galbo
Keyword(s):  
Blood Flow ◽  
Continuous Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Splanchnic Blood Flow ◽  
Dilution Method ◽  
Hepatic Glucose ◽  
Balance Technique ◽  
Tracer Dilution ◽  
Exercise In Humans

The present study compared the arteriohepatic venous (a-hv) balance technique and the tracer-dilution method for estimation of hepatic glucose production during both moderate and heavy exercise in humans. Eight healthy young men (aged 25 yr; range, 23–30 yr) performed semisupine cycling for 40 min at 50.4 ± 1.5(SE)% maximal O2 consumption, followed by 30 min at 69.0 ± 2.2% maximal O2 consumption. The splanchnic blood flow was estimated by continuous infusion of indocyanine green, and net splanchnic glucose output was calculated as the product of splanchnic blood flow and a-hv blood glucose concentration differences. Glucose appearance rate was determined by a primed, continuous infusion of [3-3H]glucose and was calculated by using formulas for a modified single compartment in non-steady state. Glucose production was similar whether determined by the a-hv balance technique or by the tracer-dilution method, both at rest and during moderate and intense exercise ( P > 0.05). It is concluded that, during exercise in humans, determination of hepatic glucose production can be performed equally well with the two techniques.

Effects of a Dobutamine-induced Increase in Splanchnic Blood Flow on Hepatic Metabolic Activity in Patients with Septic Shock 

1997 ◽  
Vol 86 (4) ◽  
pp. 818-824 ◽  
Author(s):  
Helmut Reinelt ◽  
Peter Radermacher ◽  
Gunther Fischer ◽  
Wolfgang Geisser ◽  
Ulrich Wachter ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Septic Shock ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Splanchnic Blood Flow ◽  
Volume Resuscitation ◽  
Hepatic Glucose ◽  
Splanchnic Oxygen

Background Septic shock leads to increased splanchnic blood flow (Qspl) and oxygen consumption (VO2spl). The increased Qspl, however may not match the splanchnic oxygen demand, resulting in hepatic dysfunction. This concept of ongoing tissue hypoxia that can be relieved by increasing splanchnic oxygen delivery (DO2spl), however, was challenged because most of the elevated VO2spl was attributed to increased hepatic glucose production (HGP) resulting from increased substrate delivery. Therefore the authors tested the hypothesis that a dobutamine-induced increase in Qspl and DO2spl leads to increased VO2spl associated with accelerated HGP in patients with septic shock. Methods Twelve patients with hyperdynamic septic shock in whom blood pressure had been stabilized (mean arterial pressure > or = 70 mmHg) with volume resuscitation and norepinephrine received dobutamine to obtain a 20% increase in cardiac index (CI). Qspl, DO2spl, and VO2spl were assessed using the steady-state indocyanine green clearance technique with correction for hepatic dye extraction, and HGP was determined from the plasma appearance rate of stable, non-radio-active-labeled glucose using a primed-constant infusion approach. Results Although the increase in CI resulted in a similar increase in Qspl (from 0.91 +/- 0.21 to 1.21 +/- 0.34l.min-1.m2; P < 0.001) producing a parallel increase of DO2spl (from 141 +/- 33 to 182 +/- 44 ml.min-1.m2; P < 0.001), there was no effect on VO2spl (73 +/- 16 and 82 +/- 21 ml.min-1.m2, respectively). Hepatic glucose production decreased from 5.1 +/- 1.6 to 3.6 +/- 0.9 mg.kg-1.min-1 (P < 0.001). Conclusions In the patients with septic shock in whom blood pressure had been stabilized with volume resuscitation and norepinephrine, no delivery-dependency of VO2spl could be detected. Oxygen consumption was not related to the accelerated HGP either, and thus the concept that HGP dominates VO2spl must be questioned in well-resuscitated patients with septic shock.

Regulation of hepatic glucose production during exercise in humans: role of sympathoadrenergic activity

1993 ◽  
Vol 265 (2) ◽  
pp. E275-E283 ◽  
Author(s):  
M. Kjaer ◽  
K. Engfred ◽  
A. Fernandes ◽  
N. H. Secher ◽  
H. Galbo
Keyword(s):  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Constant Infusion ◽  
Intense Exercise ◽  
Nerve Activity ◽  
Hepatic Glucose ◽  
Sympathoadrenergic Activity ◽  
Exercise In Humans

To investigate the role of sympathoadrenergic activity on glucose production (Ra) during exercise, eight healthy males bicycled 20 min at 41 +/- 2 and 74 +/- 4% maximal O2 uptake (VO2max; mean +/- SE) either without (control; Co) or with blockade of sympathetic nerve activity to liver and adrenal medulla by local anesthesia of the celiac ganglion (Bl). Epinephrine (Epi) was in some experiments infused during blockade to match (normal Epi) or exceed (high Epi) Epi levels during Co. A constant infusion of somatostatin and glucagon was given before and during exercise. At rest, insulin was infused at a rate maintaining euglycemia. During intense exercise, insulin infusion was halved to mimic physiological conditions. During exercise, Ra increased in Co from 14.4 +/- 1.0 to 27.8 +/- 3.0 mumol.min-1.kg-1 (41% VO2max) and to 42.3 +/- 5.2 (74% VO2max; P < 0.05). At 41% VO2max, plasma glucose decreased, whereas it increased during 74% VO2max. Ra was not influenced by Bl. In high Epi, Ra rose more markedly compared with control (P < 0.05), and plasma glucose did not fall during mild exercise and increased more during intense exercise (P < 0.05). Free fatty acid and glycerol concentrations were always lower during exercise with than without celiac blockade. We conclude that high physiological concentrations of Epi can enhance Ra in exercising humans, but normally Epi is not a major stimulus. The study suggests that neither sympathetic liver nerve activity is a major stimulus for Ra during exercise. The Ra response is enhanced by a decrease in insulin and probably by unknown stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

Indomethacin Stimulates Basal Glucose Production in Humans without Changes in Concentrations of Glucoregulatory Hormones

1993 ◽  
Vol 85 (6) ◽  
pp. 679-685 ◽  
Author(s):  
E. P. M. Corssmit ◽  
J. A. Romijn ◽  
E. Endert ◽  
H. P. Sauerwein
Keyword(s):  
Continuous Infusion ◽  
Control Experiment ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
C Peptide ◽  
Hepatic Glucose ◽  
Glucoregulatory Hormones

1. To investigate whether indomethacin affects basal glucose production, we measured hepatic glucose production in six healthy postabsorptive subjects on two occasions: once after administration of indomethacin (150 mg orally) and once after administration of placebo. 2. Glucose production was measured by primed, continuous infusion of [3-3H]-glucose. 3. Indomethacin administration resulted in an increase in glucose production from 10.9 (SEM 0.3) μmol min−1 kg−1 to a maximum of 16.5 (SEM 1.6) μmol min−1 kg−1 (P <0.05) within ∼1 h, whereas in the control experiment glucose production declined gradually (P <0.01) (P <0.05 indomethacin versus control). There were no differences in plasma concentrations of insulin, C-peptide and counter-regulatory hormones between the two experiments. 4. Since indomethacin administration resulted in an increase in glucose production in the absence of any changes in concentrations of glucoregulatory hormones, we conclude that indomethacin stimulates hepatic glucose production through other mechanisms.

scholarly journals Differential effects of hypothalamic long-chain fatty acid infusions on suppression of hepatic glucose production

2010 ◽  
Vol 299 (4) ◽  
pp. E633-E639 ◽  
Author(s):  
R. A. Ross ◽  
L. Rossetti ◽  
T. K. T. Lam ◽  
G. J. Schwartz
Keyword(s):  
Fatty Acid ◽  
Total Dose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Mediobasal Hypothalamus ◽  
Long Chain Fatty Acid ◽  
Potent Effect ◽  
Exogenous Glucose ◽  
Hepatic Glucose ◽  
Tracer Dilution

Our objective was to investigate whether the direct bilateral infusion of the monounsaturated fatty acid (MUFA) oleic acid (OA) within the mediobasal hypothalamus (MBH) is sufficient to reproduce the effect of administration of OA (30 nmol) in the third cerebral ventricle, which inhibits glucose production (GP) in rats. We used the pancreatic basal insulin clamp technique (plasma insulin ∼20 mU/ml) in combination with tracer dilution methodology to compare the effect of MBH OA on GP to that of a saturated fatty acid (SFA), palmitic acid (PA), and a polyunsaturated fatty acid (PUFA), linoleic acid (LA). The MBH infusion of 200 but not 40 pmol of OA was sufficient to markedly inhibit GP (by 61% from 12.6 ± 0.6 to 5.1 ± 1.6 mg·kg−1·min−1) such that exogenous glucose had to be infused at the rate of 6.0 ± 1.2 mg·kg−1·min−1 to prevent hypoglycemia. MBH infusion of PA also caused a significant decrease in GP, but only at a total dose of 4 nmol (GP 5.8 ± 1.6 mg·kg−1·min−1). Finally, MBH LA at a total dose of 0.2 and 4 nmol failed to modify GP compared with rats receiving MBH vehicle. Increased availability of OA within the MBH is sufficient to markedly inhibit GP. LA does not share the effect of OA, whereas PA can reproduce the potent effect of OA on GP, but only at a higher dose. It remains to be determined whether SFAs need to be converted to MUFAs to exert this effect or whether they activate a separate signaling pathway to inhibit GP.

Pentoxifylline inhibits basal glucose production in humans

1994 ◽  
Vol 77 (6) ◽  
pp. 2767-2772 ◽  
Author(s):  
E. P. Corssmit ◽  
J. A. Romijn ◽  
E. Endert ◽  
H. P. Sauerwein
Keyword(s):  
Continuous Infusion ◽  
Adenosine Receptor ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Volume Of Distribution ◽  
Time Interval ◽  
Xanthine Derivative ◽  
Hepatic Glucose ◽  
Glucoregulatory Hormones

Adenosine stimulates hepatic glucose production in vitro. To investigate whether pentoxifylline, a xanthine derivative that blocks the adenosine receptor, inhibits basal glucose production, we measured hepatic glucose production in eight healthy postabsorptive subjects on two occasions: during continuous infusion of pentoxifylline and, in a control study, during saline infusion. Glucose production was measured by primed continuous infusion of [3–3H]glucose. Pentoxifylline infusion resulted in an approximately 22 (volume of distribution for glucose 40 ml/kg) to approximately 46% (volume of distribution for glucose 165 ml/kg) decrease in basal glucose production within approximately 1 h (P < 0.05), whereas in the control experiment glucose production declined by only approximately 4% in this time interval (P < 0.03 pentoxifylline vs. control). There were no differences in concentrations of insulin, C peptide, glucagon, or catecholamines between the two experiments. Because pentoxifylline inhibited glucose production in the absence of any changes in concentrations of glucoregulatory hormones, we conclude that pentoxyifylline inhibits hepatic glucose production through other mechanisms, e.g., by blocking the adenosine receptor.

Glucose production during strenuous exercise in humans: role of epinephrine

1999 ◽  
Vol 276 (6) ◽  
pp. E1130-E1135 ◽  
Author(s):  
Kirsten Howlett ◽  
Mark Febbraio ◽  
Mark Hargreaves
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Peak Oxygen Uptake ◽  
Strenuous Exercise ◽  
Simultaneous Increase ◽  
Intense Exercise ◽  
Epinephrine Infusion ◽  
Hepatic Glucose ◽  
Exercise In Humans

The increase in hepatic glucose production (HGP) that occurs during intense exercise is accompanied by a simultaneous increase in epinephrine, which suggests that epinephrine may be important in regulating HGP. To further investigate this, six trained men were studied twice. The first trial [control (Con)] consisted of 20 min of cycling at 40 ± 1% peak oxygen uptake (V˙o 2 peak) followed by 20 min at 80 ± 2%V˙o 2 peak. During the second trial [epinephrine (Epi)], subjects exercised for 40 min at 41 ± 2%V˙o 2 peak. Epinephrine was infused during the latter 20 min of exercise and resulted in plasma levels similar to those measured during intense exercise in Con. Glucose kinetics were measured using a primed, continuous infusion of [3-3H]glucose. HGP was similar at rest (Con, 11.0 ± 0.5 and Epi, 11.1 ± 0.5 μmol ⋅ kg−1 ⋅ min−1). In Con, HGP increased ( P < 0.05) during exercise to 41.0 ± 5.2 μmol ⋅ kg−1 ⋅ min−1at 40 min. In Epi, HGP was similar to Con during the first 20 min of exercise. Epinephrine infusion increased ( P < 0.05) HGP to 24.0 ± 2.5 μmol ⋅ kg−1 ⋅ min−1at 40 min, although this was less ( P< 0.05) than the value in Con. The results suggest that epinephrine can increase HGP during exercise in trained men; however, epinephrine during intense exercise cannot fully account for the rise in HGP. Other glucoregulatory factors must contribute to the increase in HGP during intense exercise.

scholarly journals Glucose Turnover and Hepatocyte Glucose Production of Starved and Toxaemic Pregnant Sheep

1983 ◽  
Vol 36 (3) ◽  
pp. 271 ◽  
Author(s):  
M E Wastney ◽  
JE Wolff ◽  
R Bickerstaffe
Keyword(s):  
Continuous Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Production Rates ◽  
Hepatic Gluconeogenesis ◽  
Pregnant Sheep ◽  
Hepatic Glucose ◽  
Pregnancy Toxaemia ◽  
Maternal Glucose

Ewes bearing twins were starved for 10 days during the last month of gestation to induce ovine pregnancy toxaemia (OPT). Glucose turnover was measl,lred by a primed continuous infusion of [U_ '4C]_ and [6-3HJglucose at the end of 10 days of starvation (non-susceptible), or earlier when ewes became recumbent with OPT (susceptible). All ewes were slaughtered at the end of the infusion and hepatocytes were prepared in order to measure glucose production from different substrates. Many of the ewes had dead foetuses when slaughtered. Glucose production rates by hepatocytes with the substrates propionate, lactate or alanine were significantly less from the susceptible ewes than were those from non-susceptible ewes. These low rates were not stimulated by incubation with glucagon (10-8 M), glutamine or glycerol. Rates of glucose turnover and of hepatic glucose production from all substrates were higher for ewes with dead than with live foetuses. The data support the hypothesis that pathogenesis of OPT is related to an impairment of hepatic gluconeogenesis, and further suggest that, in starved pregnant ewes, maternal glucose production may be restrained in the presence of a live foetus.

Glucose homeostasis during exercise in humans with a liver or kidney transplant

1995 ◽  
Vol 268 (4) ◽  
pp. E636-E644 ◽  
Author(s):  
M. Kjaer ◽  
S. Keiding ◽  
K. Engfred ◽  
K. Rasmussen ◽  
B. Sonne ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Adrenocorticotropic Hormone ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Plasma Renin ◽  
Hepatic Glucose ◽  
Healthy Control ◽  
Hormone Responses ◽  
Exercise In Humans

To investigate the role of liver nerve activity on hepatic glucose production during exercise, liver-transplant subjects (LTX, n = 7, 25-62 yr, 4-18 mo postoperative) cycled for 40 min, 20 min at 52 +/- 3% (SE) maximal O2 consumption (VO2max) and 20 min at 83 +/- 1% VO2max, respectively. Kidney-transplant (KTX) and healthy control subjects (C) matched for sex and age exercised at the same %VO2max as LTX. VO2max was lower in both LTX (1.59 +/- 0.12 l/min) and KTX (1.59 +/- 0.07) than in C (2.60 +/- 0.26). At rest plasma renin and insulin were higher and plasma adrenocorticotropic hormone and cortisol lower in transplant corticosteroid-treated subjects compared with C. In LTX, hepatic glucose production (Ra) increased from 11.9 +/- 0.9 (rest) to 17.6 +/- 1.8 and 25.5 +/- 1.8 mumol.min-1.kg-1 at 52 and 82% VO2max, respectively. Peripheral glucose uptake was similar to Ra, and glucose remained at basal postabsorptive levels. During exercise the Ra increase as well as norepinephrine, insulin, and growth hormone responses were similar in LTX compared with both KTX and C. The increase in epinephrine was smaller in LTX than in C, the only group showing an increase in cortisol. The increase in plasma renin activity during exercise was attenuated in KTX compared with LTX and C. During exercise blood lactate rose more and plasma glycerol and free fatty acid levels were lower in LTX and KTX compared with C.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatility does not alter the response to a physiological increment in glucagon in the conscious dog

1994 ◽  
Vol 266 (3) ◽  
pp. E467-E478 ◽  
Author(s):  
R. L. Dobbins ◽  
S. N. Davis ◽  
D. W. Neal ◽  
C. Cobelli ◽  
A. D. Cherrington
Keyword(s):  
Continuous Infusion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Compartment Model ◽  
Time Varying ◽  
Plasma Glucagon ◽  
Glucose Kinetics ◽  
Two Compartment Model ◽  
Hepatic Glucose ◽  
Pulsatile Infusion

The present study was designed to investigate if pulsatile hyperglucagonemia of physiological magnitude has greater efficacy in stimulating hepatic glucose production than constant glucagon. Paired studies were performed in conscious dogs. After insulin and glucagon were clamped at basal concentrations for 2 h, glucagon was elevated for 4 h with either a continuous infusion or pulses having physiological frequency and amplitude. With continuous infusion, plasma glucagon concentrations increased from 56 +/- 7 to 194 +/- 27 ng/l. With pulsatile infusion, glucagon concentrations started at 53 +/- 6 ng/l and then oscillated between 157 +/- 15 and 253 +/- 28 ng/l. Plasma insulin concentrations remained constant at basal levels. Glucose production was determined using a time-varying two-compartment model for glucose kinetics and deconvolution. After 15 min, glucose production had risen from 13.6 +/- 1.1 to 53.8 +/- 3.9 mumol.kg-1.min-1 with continuous infusion and from 12.9 +/- 0.6 to 50.6 +/- 2.9 mumol.kg-1.min-1 with pulsatile infusion. After 4 h, the production had fallen to 16.1 +/- 1.2 and 17.1 +/- 0.7 mumol.kg-1.min-1. In the present animal model with insulin held constant, no difference was noted between the response to continuous or pulsatile glucagon infusion.

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