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.

Regulation of glucose turnover and hormonal responses during electrical cycling in tetraplegic humans

1996 ◽  
Vol 271 (1) ◽  
pp. R191-R199 ◽  
Author(s):  
M. Kjaer ◽  
S. F. Pollack ◽  
T. Mohr ◽  
H. Weiss ◽  
G. W. Gleim ◽  
...  
Keyword(s):  
Heart Rate ◽  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Hormonal Responses ◽  
Hepatic Glucose ◽  
Exercise Period ◽  
Exercise Activity ◽  
Beta Hydroxybutyrate

To examine the importance of blood-borne vs. neural mechanisms for hormonal responses and substrate mobilization during exercise, six spinal cord-injured tetraplegic (C5-T1) males (mean age: 35 yr, range: 24-55 yr) were recruited to perform involuntary, electrically induced cycling [functional electrical stimulation (FES)] to fatigue for 24.6 +/- 2.3 min (mean and SE), and heart rate rose from 67 +/- 7 (rest) to 107 +/- 5 (exercise) beats/min. Voluntary arm cranking in tetraplegics (ARM) and voluntary leg cycling in six matched, long-term immobilized (2-12 mo) males (Vol) served as control experiments. In FES, peripheral glucose uptake increased [12.4 +/- 1.1 (rest) to 19.5 +/- 4.3 (exercise) mumol.min-1.kg-1; P < 0.05], whereas hepatic glucose production did not change from basal values [12.4 +/- 1.4 (rest) vs. 13.0 +/- 3.4 (exercise) mumol.min-1.kg-1]. Accordingly, plasma glucose decreased [from 5.4 +/- 0.3 (rest) to 4.7 +/- 0.3 (exercise) mmol/l; P < 0.05]. Plasma glucose did not change in response to ARM or Vol. Plasma free fatty acids and beta-hydroxybutyrate decreased only in FES experiments (P < 0.05). During FES, increases in growth hormone (GH) and epinephrine and decreases in insulin concentrations were abolished. Although subnormal throughout the exercise period, norepinephrine concentrations increased during FES, and responses of heart rate, adrenocorticotropic hormone, beta-endorphin, renin, lactate, and potassium were marked. In conclusion, during exercise, activity in motor centers and afferent muscle nerves is important for normal responses of GH, catecholamines, insulin, glucose production, and lipolysis. Humoral feedback and spinal or simple autonomic nervous reflex mechanisms are not sufficient. However, such mechanisms are involved in redundant control of heart rate and neuroendocrine activity in exercise.

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.

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.

Enhanced gluconeogenesis from lactate in perfused livers after endurance training

1993 ◽  
Vol 74 (2) ◽  
pp. 782-787 ◽  
Author(s):  
K. D. Sumida ◽  
J. H. Urdiales ◽  
C. M. Donovan
Keyword(s):  
Endurance Training ◽  
Hepatic Glucose Production ◽  
Liver Perfusion ◽  
Glucose Production ◽  
Hepatic Gluconeogenesis ◽  
Bicarbonate Buffer ◽  
Hepatic Glucose ◽  
14Co2 Production ◽  
Glucose Output ◽  
And Control

The effects of endurance training (running 90 min/day at 30 m/min, 10% grade) on hepatic gluconeogenesis were studied in 24-h-fasted rats with use of the isolated liver perfusion technique. After isolation, the liver was perfused (single pass) for 30 min with Krebs-Henseleit bicarbonate buffer and fresh bovine erythrocytes (hematocrit 22–24%) with no added substrate. Subsequent to the "washout" period, the reservoir was elevated with various concentrations of lactate and [U-14C]lactate (10,000 dpm/ml) to assess hepatic glucose production. Relative flow rates were not significantly different between trained (1.94 +/- 0.05 ml/g liver) and control livers (1.91 +/- 0.05 ml/g liver). Furthermore, no significant differences were observed in perfusate pH, hematocrit, bile production, or serum alanine aminotransferase effluxing from trained or control livers. At saturating arterial lactate concentrations (> 2 mM), the maximal rate (Vmax) for hepatic glucose production was significantly higher for trained (0.91 +/- 0.04 mumol.min-1 x g liver-1) than for control livers (0.73 +/- 0.02 mumol.min-1 x g liver-1). That this reflected increased gluconeogenesis is supported by a significant elevation in the Vmax for [14C]glucose production from trained (13,150 +/- 578 dpm.min-1 x g liver-1) compared with control livers (10,712 +/- 505 dpm.min-1 x g liver-1). Significant increases were also observed in the Vmax for lactate uptake (25%), O2 consumption (19%), and 14CO2 production (23%) from endurance-trained livers. The Km for hepatic glucose output, approximately 1.05 mM lactate, was unchanged after endurance training. These findings demonstrate that chronic physical activity results in an elevated capacity for hepatic gluconeogenesis, as assessed in situ at saturating lactate concentrations.

scholarly journals Glucose turnover and recycling in unrestrained and unanesthetized 48-h-old fasting or post-absorptive newborn pigs

1984 ◽  
Vol 52 (2) ◽  
pp. 277-287 ◽  
Author(s):  
Jean-Paul Pégorier ◽  
Pierre-Henri Duée ◽  
Carlo Simoes Nunes ◽  
Jean Peret ◽  
J. Girard
Keyword(s):  
Blood Glucose Concentration ◽  
Single Injection ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Glucose Turnover ◽  
Injection Technique ◽  
Hepatic Glucose ◽  
The Mean ◽  
Newborn Pigs

1. The metabolism of glucose has been studied in 48-h-old unanesthetized fasting and post-absorptive sucking piglets.2. Both [6-3H]- and [U-14CJglucose were administered either by a single injection method or by a primed infusion technique. The rates of glucose turnover and recycling were estimated under steady-state conditions.3. The rates of glucose turnover and recycling in 48-h-old fasting or post-absorptive piglets were not statistically different when measured using the single injection technique or the printed infusion method.4. The mean (with SE) rate of glucose turnover was 65.8 (2.5) in post-absorptive and 31.1 (1–9), μ mol/kg per min in fasted newborn pigs. Glucose utilization was linearly related to blood glucose concentration; regression analysis indicated a y-intercept of 7.2, μ mol/kg per min.5. As tested by arterio-portal differences the gut was not releasing glucose or galactose in 5 h-post-absorptive sucking newborn pigs. Thus, the higher rates of glucose turnover in post-absorptive newborn pigs compared with fasting ones suggest that hepatic glucose production is enhanced in post-ahsorptive sucking piglets.6. The mean (with SE) rates of glucose recycling were four times higher in post-absorptive piglets than in tasting ones, i.e. 14.4 (1.6) and 3.7 (0.5)% of [6-3H] glucose turnover respectively. As liver glycogen was exhausted in 48-h-old sucking piglets, this suggests that hepatic glucose production results from gluconeogenesis.

Pentobarbital reduces basal liver glucose output and its insulin suppression in rats

1990 ◽  
Vol 258 (4) ◽  
pp. E701-E707 ◽  
Author(s):  
P. W. Clark ◽  
A. B. Jenkins ◽  
E. W. Kraegen
Keyword(s):  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Conscious State ◽  
Hepatic Insulin Resistance ◽  
Glucose Turnover ◽  
Pentobarbital Anesthesia ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Conscious Animals

Recent reports conflict on the effect that pentobarbital anesthesia has on basal glucose turnover in the rat. It is also unclear whether pentobarbital alters insulin suppressibility of hepatic glucose production (Ra). We examined these issues by performing basal and hyperinsulinemic euglycemic clamp studies in anesthetized and conscious animals. Ra and glucose utilization (Rd) were estimated using a steady-state infusion of 3-[3H]glucose. Pentobarbital anesthesia in normothermic rats transiently elevated plasma glucose but resulted in a sustained suppression of basal Ra (10.4 +/- 0.3 vs. conscious 13.2 +/- 0.9 mg.kg-1.min-1, P less than 0.05). In the insulin-stimulated state (110 mU/l), despite similar plasma glucose and insulin levels, clamp glucose infusion rate was significantly reduced in anesthetized animals (11.1 +/- 0.9 vs. conscious 23.6 +/- 1.3 mg.kg-1.min-1, P less than 0.001). This can be attributed to both a significantly lower insulin-stimulated Rd (15.4 +/- 1.3 vs. conscious 22.8 +/- 1.4 mg.kg-1.min-1, P less than 0.005) and reduced insulin suppression of Ra (4.3 +/- 0.8 vs. conscious -0.8 +/- 0.5 mg.kg-1.min-1, P less than 0.001; i.e., anesthetized 59% vs. conscious 100% reduction of basal Ra). Thus pentobarbital anesthesia significantly reduces basal Ra and induces hepatic insulin resistance (reduces Ra suppressibility). Pentobarbital effects are not dependent on induced hypothermia, but this exacerbates the metabolic perturbation. Caution should be used in extrapolating from the anesthetized to the conscious state.

Selective suppression of hepatic glucose output by human proinsulin in the dog

1987 ◽  
Vol 252 (2) ◽  
pp. E230-E236 ◽  
Author(s):  
M. Lavelle-Jones ◽  
M. H. Scott ◽  
O. Kolterman ◽  
A. H. Rubenstein ◽  
J. M. Olefsky ◽  
...  
Keyword(s):  
Hepatic Glucose Production ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Hepatic Glucose Output ◽  
Glucose Clamp Technique ◽  
Hepatic Glucose ◽  
The Mean ◽  
Glucose Output

By using the euglycemic glucose-clamp technique we have observed the effects of comparable low dose proinsulin and insulin infusions on isotopically determined glucose turnover in 20 anesthetized dogs. In each animal somatostatin (SRIF) infusion was used to suppress endogenous pancreatic hormone secretion and basal glucagon was replaced. Peripheral proinsulin (0.083 micrograms X kg-1 X min-1) and insulin (350 microU X kg-1 X min-1) levels 15- to 20-fold higher than insulin on a molar basis, based on previous observations that proinsulin has only 5-10% the biologic potency of insulin. Three groups of infusion studies were performed: SRIF and glucagon (n = 5); SRIF, glucagon, and proinsulin (n = 10); and SRIF, glucagon, and insulin (n = 5). The mean serum proinsulin level of 2.43 +/- 0.36 pmol/ml achieved represented a 17-fold excess compared with the mean serum insulin level of 0.14 +/- 0.03 pmol (20 +/- 4 microU/ml). At these concentrations, both hormones reduced hepatic glucose production rates by approximately 50% to 2.0 +/- 0.2 mg X kg-1 X min-1 and 1.8 +/- 0.5 mg X kg-1 X min-1, respectively. In contrast, proinsulin failed to stimulate peripheral glucose utilization, whereas insulin led to a 2.0 +/- 0.3 mg X kg-1 X min-1 increment (approximately 50% increase) in glucose uptake (P less than 0.05). Thus at low infusion rates proinsulin exerts its effect predominantly by suppressing hepatic glucose production without measurable stimulation of peripheral glucose disposal. In contrast, for a comparable degree of hepatic glucose output suppression, insulin also significantly stimulates glucose disposal.

Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs

2005 ◽  
Vol 98 (3) ◽  
pp. 930-939 ◽  
Author(s):  
Michael J. Christopher ◽  
Christian Rantzau ◽  
Glenn McConell ◽  
Bruce E. Kemp ◽  
Frank P. Alford
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Uptake ◽  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Plasma Free Fatty Acid ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
Hepatic Glucose

The separate impacts of the chronic diabetic state and the prevailing hyperglycemia on plasma substrates and hormones, in vivo glucose turnover, and ex vivo skeletal muscle (SkM) during exercise were examined in the same six dogs before alloxan-induced diabetes (prealloxan) and after 4–5 wk of poorly controlled hyperglycemic diabetes (HGD) in the absence and presence of ∼300-min phlorizin-induced (glycosuria mediated) normoglycemia (NGD). For each treatment state, the ∼15-h-fasted dog underwent a primed continuous 150-min infusion of [3-3H]glucose, followed by a 30-min treadmill exercise test (∼65% maximal oxygen capacity), with SkM biopsies taken from the thigh (vastus lateralis) before and after exercise. In the HGD and NGD states, preexercise hepatic glucose production rose by 130 and 160%, and the metabolic clearance rate of glucose (MCRg) fell by 70 and 37%, respectively, compared with the corresponding prealloxan state, but the rates of glucose uptake into peripheral tissues (Rdtissue) and total glycolysis (GF) were unchanged, despite an increased availability of plasma free fatty acid in the NGD state. Exercise-induced increments in hepatic glucose production, Rdtissue, and plasma-derived GF were severely blunted by ∼30–50% in the NGD state, but increments in MCRg remained markedly reduced by ∼70–75% in both diabetic states. SkM intracellular glucose concentrations were significantly elevated only in the HGD state. Although Rdtissue during exercise in the diabetic states correlated positively with preexercise plasma glucose and insulin and GF and negatively with preexercise plasma free fatty acid, stepwise regression analysis revealed that an individual's preexercise glucose and GF accounted for 88% of Rdtissue during exercise. In conclusion, the prevailing hyperglycemia in poorly controlled diabetes is critical in maintaining a sufficient supply of plasma glucose for SkM glucose uptake during exercise. During phlorizin-induced NGD, increments in both Rdtissue and GF are impaired due to a diminished fuel supply from plasma glucose and a sustained reduction in increments of MCRg.

Thermogenesis and fructose metabolism in humans

1992 ◽  
Vol 262 (5) ◽  
pp. E591-E598 ◽  
Author(s):  
J. M. Schwarz ◽  
K. J. Acheson ◽  
L. Tappy ◽  
V. Piolino ◽  
M. J. Muller ◽  
...  
Keyword(s):  
Energy Cost ◽  
Hepatic Glucose Production ◽  
Resting Metabolic Rate ◽  
Glucose Production ◽  
Glucose Turnover ◽  
Elevated Plasma ◽  
Fructose Metabolism ◽  
Euglycemic Clamp ◽  
Hepatic Glucose ◽  
Thermic Effect

Resting metabolic rate was measured in 10 healthy volunteers (25 yr, 73 kg, 182 cm) for 1 h before and 4 h during intravenous (iv) fructose administration (20% at 50 mumol.kg-1.min-1) with (+P) or without (-P) propranolol (100 micrograms/kg, 1 microgram.kg-1.min-1) during the last 2 h. Some subjects were studied a further 2 h with fructose infusion and +P or -P in hyperinsulinemic (2.9 pmol.kg-1.min-1) euglycemic conditions. Glucose turnover ([3-3H]glucose, 20 muCi bolus and 0.2 muCi/min) was calculated over 30 min at 0, 2, 4, and 6 h. The thermic effect of iv fructose was approximately 7.5% and decreased to 4.9 +/- 0.4% (P less than 0.01) +P. During the euglycemic clamp the thermic effect was 6.2 +/- 0.9% (-P) and 5.3 +/- 0.9% (+P). Hepatic glucose production (HGP) was 11.7 mumol.kg-1.min-1 (0 h) and did not change after 2 h iv fructose (11.8 +/- 0.5 and 9.8 +/- 0.6 mumol.kg-1.min-1 -P and +P, respectively) but increased to 13.8 +/- 0.9 (-P) and 12.9 +/- 0.8 mumol.kg-1.min-1 (+P) (P less than 0.01) after 4 h. HGP was suppressed to varying degrees during the euglycemic clamp. It is concluded that 1) the greater thermic effect of fructose compared with glucose is probably due to continued gluconeogenesis (which is suppressed by glucose or glucose-insulin) and the energy cost of fructose metabolism to glucose in the liver. 2) There is a sympathetically mediated component to the thermic effect of fructose (approximately 30%) that is not mediated by elevated plasma insulin concentrations similar to those observed with iv glucose.

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