Role of liver nerves and adrenal medulla in glucose turnover of running rats

1985 ◽  
Vol 59 (5) ◽  
pp. 1640-1646 ◽  
Author(s):  
B. Sonne ◽  
K. J. Mikines ◽  
E. A. Richter ◽  
N. J. Christensen ◽  
H. Galbo
Keyword(s):  
Glucose Production ◽  
Constant Infusion ◽  
Moderate Intensity ◽  
Glucose Turnover ◽  
Hepatic Glycogen ◽  
Turnover Rates ◽  
Glycogen Depletion ◽  
And Control ◽  
Liver Nerves

Sympathetic control of glucose turnover was studied in rats running 35 min at 21 m X min-1 on the level. The rats were surgically liver denervated, adrenodemedullated, or sham operated. Glucose turnover was measured by primed constant infusion of [3–3H]glucose. At rest, the three groups had identical turnover rates and concentrations of glucose in plasma. During running, glucose production always rose rapidly to steady levels. The increase was not influenced by liver denervation but was halved by adrenodemedullation. Similarly, hepatic glycogen depletion was identical in denervated and control rats but reduced after adrenodemedullation. Early in exercise, glucose uptake rose identically in all groups and, in adrenodemedullated rats, matched glucose production. Accordingly, plasma glucose concentration increased in liver-denervated and control rats but was constant in adrenodemedullated rats. Compensatory changes in hormone or substrate levels explaining the lack of effect of liver denervation were not found. In rats with intact adrenals, the plasma epinephrine concentration was increased after 2.5 min of running. It is concluded that, in rats carrying out exercise of moderate intensity and duration, hepatic glycogenolysis and glucose production are not influenced by the autonomic liver nerves but are enhanced by circulating epinephrine.

Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats

1985 ◽  
Vol 248 (3) ◽  
pp. E327-E332
Author(s):  
K. J. Mikines ◽  
B. Sonne ◽  
E. A. Richter ◽  
N. J. Christensen ◽  
H. Galbo
Keyword(s):  
Glucose Production ◽  
Glucose Turnover ◽  
Hepatic Glycogen ◽  
Autonomic Nerves ◽  
Glycogen Depletion ◽  
Glucose Clearance ◽  
Glucose Recovery ◽  
Acute Hypoglycemia ◽  
And Control

The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetized as well as in chronically catheterized, awake rats. Half of the anesthetized denervated or sham-operated rats had previously been adrenodemedullated. Glucose turnover was measured by primed, constant intravenous infusion of [3-3H]glucose. Before as well as during hypoglycemia the arterial glucose concentration and rates of production and utilization of glucose were similar in denervated rats and control rats. Also hepatic glycogen depletion was similar in the groups. The lack of effect of denervation could not be ascribed to compensating changes in hormone or substrate levels. In adrenodemedullated rats lack of glucose recovery from hypoglycemia was accompanied by delayed normalization of glucose clearance. In fed rats, activity in hepatic autonomic nerves is not a primary mechanism increasing glucose production during acute hypoglycemia. Epinephrine enhances glucose recovery by decreasing glucose clearance rather than by increasing glucose production, at least when glucagon is present.

Experimental validation of measurements of glucose turnover in nonsteady state.

1978 ◽  
Vol 234 (1) ◽  
pp. E84 ◽  
Author(s):  
J Radziuk ◽  
K H Norwich ◽  
M Vranic
Keyword(s):  
Dispersion Model ◽  
Glucose Production ◽  
Compartment Model ◽  
Sole Source ◽  
Volume Of Distribution ◽  
Endogenous Glucose Production ◽  
The Body ◽  
Glucose Turnover ◽  
Turnover Rates ◽  
Nonsteady State

The aim of the present experiments is to validate, in conscious dogs, the tracer infusion methods of measuring nonsteady turnover rates. This was done in nine experiments performed in four normal dogs by infusing isotopically labeled glucose (2-3H, 6-3H, 1-14C) and monitoring the concentrations of both the labeled and unlabeled substances. The validation is based on the observation that a high exogenous infusion of glucose will suppress endogenous glucose production and become the sole source of glucose in the body. By infusing glucose at a high, time-varying rate, calculating its rate of appearance, (Ra) and comparing it to the infused rate, the method can be verified. The calculations were based on: a) a single-compartment model with a modified volume of distribution; b) a two-compartment model; and c) a generalized dispersion model. The absolute values of the areas of the deviations of the calculated from the infused curves were found to be, respectively, 9.5, 8.4, and 7.8 percent of the total area under the infused curve. It was concluded that the tracer infusion method can reliably measure Ra of glucose when it is changing rapidly, and the system is out of steady state.

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)

Role of glucagon in countering hypoglycemia induced by insulin infusion in dogs

1991 ◽  
Vol 261 (6) ◽  
pp. E773-E781 ◽  
Author(s):  
R. L. Dobbins ◽  
C. C. Connolly ◽  
D. W. Neal ◽  
L. J. Palladino ◽  
A. F. Parlow ◽  
...  
Keyword(s):  
Insulin Infusion ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Glucose Turnover ◽  
Major Contributor ◽  
Normal Response ◽  
Counterregulatory Hormones ◽  
Exogenous Glucose ◽  
Experimental Protocols

The aim of the present study was to characterize the role of glucagon in countering the prolonged hypoglycemia resulting from insulin infusion and to determine whether its effect is manifest through glycogenolysis and/or gluconeogenesis. Two groups of 18-h fasted somatostatin-treated dogs were given intraportal insulin at 5 mU.kg-1.min-1. In one group (SimGGN; n = 6), glucagon was infused intraportally so as to mimic the normal response to hypoglycemia. In a second group (BasGGN; n = 6), glucagon was infused at a basal rate. Glucose turnover and gluconeogenesis were assessed by combining tracer and hepatic balance techniques. Exogenous glucose was infused as needed to maintain equivalent hypoglycemia at approximately 45 mg/dl in the two groups. Although glucagon concentrations were significantly different, the levels of other counterregulatory hormones were equivalent in both experimental protocols. Endogenous glucose production (EGP) in SimGGN doubled from 2.4 +/- 0.2 to 5.4 +/- 0.8 mg.kg-1.min-1 by 1 h before dropping to 4.5 +/- 0.2 mg.kg-1.min-1 in the 3rd h of insulin infusion. EGP in BasGGN was initially 2.5 +/- 0.1 mg.kg-1.min-1, unchanged by 1 h, and increased to 3.9 +/- 0.2 mg.kg-1.min-1 by the 3rd h of insulin infusion. In the 1st h of insulin infusion, the rise in gluconeogenesis in both groups was equal and represented only a small part of total EGP. By the 3rd h, gluconeogenesis was the major contributor to total EGP, and gluconeogenic efficiency increased significantly more in SimGGN than BasGGN (261 vs. 140%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Ketone-body metabolism in tumour-bearing rats

1986 ◽  
Vol 233 (2) ◽  
pp. 485-491 ◽  
Author(s):  
A M Rofe ◽  
R Bais ◽  
R A Conyers
Keyword(s):  
Blood Glucose ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Hepatic Glycogen ◽  
Turnover Rates ◽  
Total Blood ◽  
Normal Tissues ◽  
Tumour Bearing ◽  
And Control

During starvation for 72 h, tumour-bearing rats showed accelerated ketonaemia and marked ketonuria. Total blood [ketone bodies] were 8.53 mM and 3.34 mM in tumour-bearing and control (non-tumour-bearing) rats respectively (P less than 0.001). The [3-hydroxybutyrate]/[acetoacetate] ratio was 1.3 in the tumour-bearing rats, compared with 3.2 in the controls at 72 h (P less than 0.001). Blood [glucose] and hepatic [glycogen] were lower at the start of starvation in tumour-bearing rats, whereas plasma [non-esterified fatty acids] were not increased above those in the control rats during starvation. After functional hepatectomy, blood [acetoacetate], but not [3-hydroxybutyrate], decreased rapidly in tumour-bearing rats, whereas both ketone bodies decreased, and at a slower rate, in the control rats. Blood [glucose] decreased more rapidly in the hepatectomized control rats. Hepatocytes prepared from 72 h-starved tumour-bearing and control rats showed similar rates of ketogenesis from palmitate, and the distribution of [1-14C] palmitate between oxidation (ketone bodies and CO2) and esterification was also unaffected by tumour-bearing, as was the rate of gluconeogenesis from lactate. The carcinoma itself showed rapid rates of glycolysis and a poor ability to metabolize ketone bodies in vitro. The results are consistent with the peripheral, normal, tissues in tumour-bearing rats having increased ketone-body and decreased glucose metabolic turnover rates.

scholarly journals Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Relation of catecholamine actions to thyroid activity in controlling glucose turnover

1979 ◽  
Vol 182 (2) ◽  
pp. 585-592 ◽  
Author(s):  
F Okajima ◽  
M Ui
Keyword(s):  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Rate Coefficients ◽  
Glucose Turnover ◽  
Turnover Rates ◽  
Beta Adrenergic ◽  
Thyroid State ◽  
Adrenergic Antagonist ◽  
6 Hydroxydopamine

1. In euthyroid rats, treatment with reserpine of 6-hydroxydopamine, which deprived neuronal terminals of catecholamines, resulted in increases in rates and rate coefficients for blood glucose turnover in the starved states as determined by decay of [U-14C,6-3H]-glucose. Conversely, the injection of adrenaline or noradrenaline into starved euthyroid rats caused a marked decrease in rate coeeficients for glucose turnover. There was no change in the percentage glucose recycling under these conditions. 2. Adrenaline and noradrenaline caused more pronounced hyperglycaemia in hyperthyroid than in euthyroid rats owing to the greater activation of hepatic glucose production. 3. The increase in glucose turnover characteristics of hyperthyroidism was observed even after treatment with an alpha- or beta-adrenergic antagonist, showing the insignificant role of the balance between alpha- and beta-adrenergic receptors in the thyroid-dependent metabolic changes. 4. Rate coefficients for glucose turnover were not affected by reserpine treatment or catecholamine injections when rats had been rendered hyperthyroid. 5. Thus catecholamines are direct determinants of glucose-turnover rates in the starved state, and depend to some extent on the prevailing thyroid state.

Hepatic glycogen in humans. II. Gluconeogenetic formation after oral and intravenous glucose

1989 ◽  
Vol 257 (2) ◽  
pp. E158-E169 ◽  
Author(s):  
J. Radziuk
Keyword(s):  
Human Subjects ◽  
Glucose Production ◽  
Glucose Infusion ◽  
Constant Infusion ◽  
Hepatic Glycogen ◽  
Oral Glucose ◽  
Intravenous Glucose ◽  
Glucose Loading ◽  
Glucose Administration

The amount of glycogen that is formed by gluconeogenetic pathways during glucose loading was quantitated in human subjects. Oral glucose loading was compared with its intravenous administration. Overnight-fasted subjects received a constant infusion or [3-3H]glucose and a marker for gluconeogenesis, [U-14C]lactate or sodium [14C]bicarbonate [14C]bicarbonate). An unlabeled glucose load was then administered. Postabsorptively, or after glucose infusion was terminated, a third tracer ([6-3H]glucose) infusion was initiated along with a three-step glucagon infusion. Without correcting for background stimulation of [14C]glucose production or for dilution of 14C with citric acid cycle carbon in the oxaloacetate pool, the amount of glycogen mobilized by the glucagon infusion that was produced by gluconeogenesis during oral glucose loading was 2.9 +/- 0.7 g calculated from [U-14C]-lactate incorporation and 7.4 +/- 1.3 g calculated using [14C]bicarbonate as a gluconeogenetic marker. During intravenous glucose administration the latter measurement also yielded 7.2 +/- 1.1 g. When the two corrections above are applied, the respective quantities became 5.3 +/- 1.7 g for [U-14C]lactate as tracer and 14.7 +/- 4.3 and 13.9 +/- 3.6 g for oral and intravenous glucose with [14C]bicarbonate as tracer (P less than 0.05, vs. [14C]-lactate as tracer). When [2-14C]acetate was infused, the same amount of label was incorporated into mobilized glycogen regardless of which route of glucose administration was used. Comparison with previous data also suggests that 14CO2 is a potentially useful marker for the gluconeogenetic process in vivo.

Accelerated glycogenolysis in uremia and under sucrose feeding: role of phosphorylase alpha regulators

1997 ◽  
Vol 273 (1) ◽  
pp. E17-E27
Author(s):  
Z. Bakkour ◽  
D. Laouari ◽  
S. Dautrey ◽  
J. P. Yvert ◽  
C. Kleinknecht
Keyword(s):  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Glycogen Storage ◽  
Hepatic Insulin Resistance ◽  
Hepatic Glycogen ◽  
Glycogen Depletion ◽  
Sucrose Feeding

To understand the mechanism of hepatic glycogen depletion found in uremia and under sucrose feeding, we examined net hepatic glycogenolysis-associated active enzymes and metabolites during fasting. Liver was taken 2, 7, and 18 h after food removal in uremic and pair-fed control rats fed either a sucrose or cornstarch diet for 21 days. Other uremic and control rats fasted for 18 h were refed a sucrose meal to measure glycogen increment. Glycogen storage in uremia was normal, suggesting effective glycogen synthesis. During a short fast, sucrose feeding and uremia enhanced net glycogenolysis through different but additive mechanisms. Under sucrose feeding, there were high phosphorylase alpha levels associated with hepatic insulin resistance. In uremia, phosphorylase alpha levels were low, but the enzyme was probably activated in vivo by a fall of inhibitors (ATP, alpha-glycerophosphate, fructose-1,6-diphosphate, and glucose) and a rise of Pi, as verified in vitro. Enhanced gluconeogenesis was also suggested, but excessive hepatic glucose production was unlikely in uremia. During fasting, hypoglycemia occurred in uremia due to reduced glycogenolysis, inefficient hepatic gluconeogenesis, and impaired renal gluconeogenesis. This may be relevant to poor fasting tolerance in uremia, which could be aggravated under excessive sucrose intake.

Menstrual cycle phase and sex influence muscle glycogen utilization and glucose turnover during moderate-intensity endurance exercise

2006 ◽  
Vol 291 (4) ◽  
pp. R1120-R1128 ◽  
Author(s):  
Michaela C. Devries ◽  
Mazen J. Hamadeh ◽  
Stuart M. Phillips ◽  
Mark A. Tarnopolsky
Keyword(s):  
Menstrual Cycle ◽  
Endurance Exercise ◽  
Muscle Glycogen ◽  
Constant Infusion ◽  
Moderate Intensity ◽  
Glucose Turnover ◽  
Cycle Phase ◽  
Metabolic Clearance ◽  
Menstrual Cycle Phase ◽  
Glycogen Utilization

Numerous studies from our and other laboratories have shown that women have a lower respiratory exchange ratio (RER) during exercise than equally trained men, indicating a greater reliance on fat oxidation. Differences in estrogen concentration between men and women likely play a role in this sex difference. Differing estrogen and progesterone concentrations during the follicular (FP) and luteal (LP) phases of the female menstrual cycle suggest that fuel use may also vary between phases. The purpose of the current study was to determine the effect of menstrual cycle phase and sex upon glucose turnover and muscle glycogen utilization during endurance exercise. Healthy, recreationally active young women ( n = 13) and men ( n = 11) underwent a primed constant infusion of [6,6-2H]glucose with muscle biopsies taken before and after a 90-min cycling bout at 65% peak O2 consumption. LP women had lower glucose rate of appearance (Ra, P = 0.03), rate of disappearance (Rd, P = 0.03), and metabolic clearance rate (MCR, P = 0.04) at 90 min of exercise and lower proglycogen ( P = 0.04), macroglycogen ( P = 0.04), and total glycogen ( P = 0.02) utilization during exercise compared with FP women. Men had a higher RER ( P = 0.02), glucose Ra ( P = 0.03), Rd ( P = 0.03), and MCR ( P = 0.01) during exercise compared with FP women, and men had a higher RER at 75 and 90 min of exercise ( P = 0.04), glucose Ra ( P = 0.01), Rd ( P = 0.01), and MCR ( P = 0.001) and a greater PG utilization ( P = 0.05) compared with LP women. We conclude that sex, and to a lesser extent menstrual cycle, influence glucose turnover and glycogen utilization during moderate-intensity endurance exercise.

scholarly journals Effects of β-adrenergic blockade on hepatic and renal glucose production during hypoglycemia in conscious dogs

1998 ◽  
Vol 275 (5) ◽  
pp. E792-E797
Author(s):  
Eugenio Cersosimo ◽  
Irina N. Zaitseva ◽  
Mohamed Ajmal
Keyword(s):  
Glucose Production ◽  
Constant Infusion ◽  
Hepatic Veins ◽  
Adrenergic Blockade ◽  
Flow Probe ◽  
Before And After ◽  
Liver And Kidney ◽  
Arteriovenous Difference ◽  
Arterial Glucose

To investigate the role of β-adrenergic mechanisms in the counterregulatory response of the liver and kidney to hypoglycemia, we studied 10 dogs before and after a 2-h constant infusion of insulin (4 mU ⋅ kg−1 ⋅ min−1) either without ( n = 4) or with (8 μg/min, n = 6) propranolol and variable dextrose to maintain hypoglycemia, 7 days after surgical placement of sampling catheters in left renal and hepatic veins and femoral artery. Systemic glucose appearance (Ra) and endogenous (EGP), hepatic (HGP), and renal (RGP) glucose production were measured by a combination of arteriovenous difference and peripheral infusion of [6-3H]glucose, renal blood flow with a flow probe, and hepatic plasma flow by indocyanine green clearance. Without β-adrenergic blockade, arterial glucose decreased from 5.12 ± 0.02 to 2.53 ± 0.07 mmol/l, glucose Ra increased from 17.8 ± 0.7 to 30.5 ± 2.5 ( P< 0.01) when EGP was 22.2 ± 0.5, HGP from 13.5 ± 1.1 to 19.3 ± 1.3, and RGP from 2.4 ± 1.0 to 8.6 ± 0.9 μmol ⋅ kg−1 ⋅ min−1(all P < 0.05). When propranolol was infused, glucose decreased from 5.97 ± 0.02 to 2.71 ± 0.03 mmol/l, glucose Ra increased from 16.3 ± 1.0 to 25.1 ± 1.6 when EGP was 9.9 ± 0.4, HGP decreased from 14.4 ± 0.7 to 10.4 ± 0.6, and RGP decreased from 3.8 ± 1.3 to 1.1 ± 0.8 μmol ⋅ kg−1 ⋅ min−1(all P < 0.05). Our data indicate that β-adrenergic blockade impairs glucose recovery during sustained hypoglycemia, in part, by preventing the simultaneous compensatory increase in HGP and RGP.

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