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.

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.

Effect of somatostatin on plasma glucagon and insulin, and glucose turnover in exercising sheep

1979 ◽  
Vol 47 (2) ◽  
pp. 273-278 ◽  
Author(s):  
R. P. Brockman
Keyword(s):  
Insulin Secretion ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Strenuous Exercise ◽  
Glucose Turnover ◽  
Moderate Exercise ◽  
Plasma Glucagon ◽  
Hepatic Glucose ◽  
Exercise Induced ◽  
Glucagon And Insulin

To examine the roles of glucagon and insulin in exercise, four sheep were run on a treadmill with and without simultaneous infusion of somatostatin (SRIF), a peptide that suppresses glucagon and insulin secretion. SRIF infusion suppressed the exercise-induced rise in plasma glucagon during both moderate (5--5.5 km/h) and strenuous exercise (7.0 km/h). In addition, SRIF prevented the rise insulin concentrations during moderate exercise. During strenuous exercise, insulin concentrations were depressed in both groups. The infusion of SRIF was associated with a reduction in exercise-induced glucose production, as determined by infusion of [6–3H]glucose, during the first 15 min of both moderate and strenuous exercise compared to controls. Beyond 15 min glucose production was not significantly altered by SRIF infusions. These data are consistent with glucagon having an immediate, but only transient, stimulatory effect on the exercise-induced hepatic glucose production.

Effect of carbohydrate ingestion on glucose kinetics during exercise in the heat

2001 ◽  
Vol 90 (2) ◽  
pp. 601-605 ◽  
Author(s):  
Damien J. Angus ◽  
Mark A. Febbraio ◽  
David Lasini ◽  
Mark Hargreaves
Keyword(s):  
Heart Rate ◽  
Relative Humidity ◽  
Respiratory Exchange Ratio ◽  
Glucose Solution ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Peak Oxygen Uptake ◽  
Glucose Kinetics ◽  
Carbohydrate Ingestion ◽  
Hepatic Glucose

Six endurance-trained men [peak oxygen uptake (V˙o 2) = 4.58 ± 0.50 (SE) l/min] completed 60 min of exercise at a workload requiring 68 ± 2% peak V˙o 2 in an environmental chamber maintained at 35°C (<50% relative humidity) on two occasions, separated by at least 1 wk. Subjects ingested either a 6% glucose solution containing 1 μCi [3-3H]glucose/g glucose (CHO trial) or a sweet placebo (Con trial) during the trials. Rates of hepatic glucose production [HGP = glucose rate of appearance (Ra) in Con trial] and glucose disappearance (Rd), were measured using a primed, continuous infusion of [6,6-2H]glucose, corrected for gut-derived glucose (gut Ra) in the CHO trial. No differences in heart rate, V˙o 2, respiratory exchange ratio, or rectal temperature were observed between trials. Plasma glucose concentrations were similar at rest but increased ( P < 0.05) to a greater extent in the CHO trial compared with the Con trial. This was due to the absorption of ingested glucose in the CHO trial, because gut Ra after 30 and 50 min (16 ± 5 μmol · kg−1 · min−1) was higher ( P < 0.05) compared with rest, whereas HGP during exercise was not different between trials. Glucose Rd was higher ( P < 0.05) in the CHO trial after 30 and 50 min (48.0 ± 6.3 vs 34.6 ± 3.8 μmol · kg−1 · min−1, CHO vs. Con, respectively). These results indicate that ingestion of carbohydrate, at a rate of ∼1.0 g/min, increases glucose Rd but does not blunt the rise in HGP during exercise in the heat.

scholarly journals Chronic anemic hypoxemia increases plasma glucagon and hepatic PCK1 mRNA in late-gestation fetal sheep

2016 ◽  
Vol 311 (1) ◽  
pp. R200-R208 ◽  
Author(s):  
Christine Culpepper ◽  
Stephanie R. Wesolowski ◽  
Joshua Benjamin ◽  
Jennifer L. Bruce ◽  
Laura D. Brown ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Late Gestation ◽  
Hepatic Glycogen ◽  
Plasma Glucagon ◽  
Low Oxygen ◽  
Fetal Sheep ◽  
Hepatic Glucose ◽  
Arterial Plasma

Hepatic glucose production (HGP) normally begins just prior to birth. Prolonged fetal hypoglycemia, intrauterine growth restriction, and acute hypoxemia produce an early activation of fetal HGP. To test the hypothesis that prolonged hypoxemia increases factors which regulate HGP, studies were performed in fetuses that were bled to anemic conditions (anemic: n = 11) for 8.9 ± 0.4 days and compared with control fetuses ( n = 7). Fetal arterial hematocrit and oxygen content were 32% and 50% lower, respectively, in anemic vs. controls ( P < 0.005). Arterial plasma glucose was 15% higher in the anemic group ( P < 0.05). Hepatic mRNA expression of phosphonenolpyruvate carboxykinase ( PCK1) was twofold higher in the anemic group ( P < 0.05). Arterial plasma glucagon concentrations were 70% higher in anemic fetuses compared with controls ( P < 0.05), and they were positively associated with hepatic PCK1 mRNA expression ( P < 0.05). Arterial plasma cortisol concentrations increased 90% in the anemic fetuses ( P < 0.05), but fetal cortisol concentrations were not correlated with hepatic PCK1 mRNA expression. Hepatic glycogen content was 30% lower in anemic vs. control fetuses ( P < 0.05) and was inversely correlated with fetal arterial plasma glucagon concentrations. In isolated primary fetal sheep hepatocytes, incubation in low oxygen (3%) increased PCK1 mRNA threefold compared with incubation in normal oxygen (21%). Together, these results demonstrate that glucagon and PCK1 may potentiate fetal HGP during chronic fetal anemic hypoxemia.

Effects of sustained swimming on hepatic glucose production of rainbow trout

1999 ◽  
Vol 202 (16) ◽  
pp. 2161-2166 ◽  
Author(s):  
D.S. Shanghavi ◽  
J.M. Weber
Keyword(s):  
Rainbow Trout ◽  
Glucose Utilization ◽  
Blood Glucose Concentration ◽  
Hepatic Glucose Production ◽  
Mammalian Species ◽  
Glucose Production ◽  
Glucose Kinetics ◽  
Fourfold Increase ◽  
Rainbow Trout Oncorhynchus Mykiss ◽  
Hepatic Glucose

The rate of hepatic glucose production (R(a)glucose) was measured by continuous infusions of 6-[(3)H]glucose in live rainbow trout (Oncorhynchus mykiss) before, during and after swimming for 3 h at 1.5 body lengths s(−)(1) in a swim tunnel. Contrary to expectation, we found that sustained swimming causes a 33 % decline in the R(a),(glucose) of trout (from 7.6+/−2.1 to 5.1+/−1.3 (μ)mol kg(−)(1)min(−)(1), means +/− s.e.m., N=7), even though exercise of the same intensity elicits a two- to fourfold increase in all the mammalian species investigated to date. Measurements of catecholamine levels show that circulating [epinephrine] decreases by 30 % during exercise (from 4.7+/−0.3 to 3.3+/−0.4 nmol l(−)(1), N=8), suggesting that this hormone is partly responsible for controlling the decline in R(a)glucose. The inhibiting effect of swimming on hepatic glucose production persists for at least 1 h after the cessation of exercise. In addition, rainbow trout can maintain a steady blood glucose concentration throughout sustained exercise by closely matching hepatic glucose production with peripheral glucose utilization, even though this species is generally considered to be a poor glucoregulator. This study provides the first continuous measurements of glucose kinetics during the transition from rest to work in an ectotherm and it suggests that circulating glucose is not an important fuel for aerobic locomotion in trout.

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.

Non-steady state: error analysis of Steele's model and developments for glucose kinetics

1987 ◽  
Vol 252 (5) ◽  
pp. E679-E689 ◽  
Author(s):  
C. Cobelli ◽  
A. Mari ◽  
E. Ferrannini
Keyword(s):  
Steady State ◽  
Time Course ◽  
Specific Activity ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Kinetics ◽  
New Model ◽  
Average Value ◽  
Hepatic Glucose ◽  
Mean Glucose

The model proposed by Steele (Ann. NY Acad. Sci. 82: 420-430, 1959) to compute rates of appearance and disappearance in non-steady state is subjected to theoretical analysis. It is shown that this model introduces an error with two components, one dependent on the volume of the compartment, the other related to the complex configuration of the system. The errors depend on the time course of specific activity, change differently with time, and may take the opposite sign but they do not, in general, cancel each other. Corollaries of this analysis are the following: there is no single pool-fraction value satisfactory under all non-steady-state situations; keeping tracer specific activity as constant as possible during the experiment minimizes both errors; and non-steady-state analysis demands proper modeling of the system. Tracer experiments were carried out in five normal volunteers. Plasma [3-3H]glucose concentration was first brought to equilibrium by means of a primed constant 2-h infusion, and then the steady state was perturbed by a 2-h euglycemic insulin (1 mU X min-1 X kg-1) clamp, realizing a transition between a basal and a euglycemic hyperinsulinemic steady state. These data were analyzed with Steele's equation, the two compartment models of Radziuk et al. [Am. J. Physiol. 234 (Endocrinol. Metab. Gastrointest. Physiol. 3): E84-E93, 1978], and a new model based on a study on glucose kinetics carried out in the two steady states separately. Steele's equation yielded negative values for hepatic glucose production already 40 min into the clamp and throughout the study. The average value of glucose production during the 2nd h was -0.88 mg X min-1 X kg-1; the suppression of basal release over the 2-h period was 115%. In contrast, the new model calculated a mean glucose production of 0.37 mg X min-1 X kg-1 during the 2nd h and an overall suppression of 62%; no negative values were obtained.

Evidence against important catecholamine compensation for absent glucagon counterregulation

1991 ◽  
Vol 260 (2) ◽  
pp. E203-E212 ◽  
Author(s):  
P. De Feo ◽  
G. Perriello ◽  
E. Torlone ◽  
C. Fanelli ◽  
M. M. Ventura ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Plasma Glucagon ◽  
Counterregulatory Hormones ◽  
Exogenous Glucose ◽  
Hepatic Glucose ◽  
Clamp Study

To assess the counterregulatory role of glucagon and to test the hypothesis that catecholamines can largely compensate for an impaired glucagon response, four studies were performed in seven normal volunteers. In all studies, insulin was infused subcutaneously (15 mU.m-2.min-1) and increased circulating insulin approximately twofold to levels (26 +/- 1 microU/ml) observed with intensive insulin therapy. In study 1, plasma glucose fluxes (D-[3-3H]glucose) and plasma substrate and counterregulatory hormone concentrations were simply monitored; plasma glucose decreased from 87 +/- 2 mg/dl and plateaued at 51 +/- 2 mg/dl for 3 h. In study 2 [pituitary-adrenal-pancreatic (PAP) clamp], secretion of insulin and counterregulatory hormones (except for catecholamines) was prevented by somatostatin (0.5 mg/h i.v.) and metyrapone (0.5 g/4 h per os), and glucagon, cortisol, and growth hormone were reinfused to reproduce the concentrations of study 1. In study 3 (lack of glucagon response), the PAP clamp was performed with maintenance of plasma glucagon at basal levels, and glucose was infused whenever needed to reproduce plasma glucose concentration of study 2. Study 4 was identical to study 3, but exogenous glucose was not infused. The PAP clamp (study 2) reproduced glucose concentrations and fluxes observed in study 1. In studies 3 and 4, isolated lack of glucagon response did not affect glucose utilization but caused an early and persistent decrease in hepatic glucose production (approximately 60%) that caused plasma glucose to decrease to 38 +/- 2 mg/dl (P less than 0.01 vs. control 62 +/- 2 mg/dl), despite compensatory increases in plasma epinephrine. We conclude that, in a model of clinical hypoglycemia, glucagon's effect on hepatic glucose production is a dominant counterregulatory factor in humans and that its absence cannot be compensated for by increased epinephrine secretion.

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