Effect of fasting on the intracellular metabolic partition of intravenously infused glucose in humans

1999 ◽  
Vol 277 (5) ◽  
pp. E815-E823 ◽  
Author(s):  
F. Fery ◽  
L. Plat ◽  
E. O. Balasse
Keyword(s):  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
Normal Subjects ◽  
Glucose Disposal ◽  
Indirect Pathway ◽  
Total Carbohydrate ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Direct Pathway ◽  
Group 3 ◽  
Group 2

The effects of fasting on the pathways of insulin-stimulated glucose disposal were explored in three groups of seven normal subjects. Group 1 was submitted to a euglycemic hyperinsulinemic clamp (∼100 μU/ml) after both a 12-h and a 4-day fast. The combined use of [3-3H]- and [U-14C]glucose allowed us to demonstrate that fasting inhibits, by ∼50%, glucose disposal, glycolysis, glucose oxidation, and glycogen synthesis via the direct pathway. In group 2, in which the clamp glucose disposal during fasting was restored by hyperglycemia (155 ± 15 mg/dl), fasting stimulated glycogen synthesis (+29 ± 2%) and inhibited glycolysis (−32 ± 3%) but only in its oxidative component (−40 ± 3%). Results were similar in group 3 in which the clamp glucose disposal was restored by a pharmacological elevation of insulin (∼2,800 μU/ml), but in this case, both glycogen synthesis and nonoxidative glycolysis participated in the rise in nonoxidative glucose disposal. In all groups, the reduction in total carbohydrate oxidation (indirect calorimetry) induced by fasting markedly exceeded the reduction in circulating glucose oxidation, suggesting that fasting also inhibits intracellular glycogen oxidation. Thus prior fasting favors glycogen retention by three mechanisms: 1) stimulation of glycogen synthesis via the direct pathway; 2) preferential inhibition of oxidative rather than nonoxidative glycolysis, thus allowing carbon conservation for glycogen synthesis via the indirect pathway; and 3) suppression of intracellular glycogen oxidation.

Active head movements facilitate compensation for effects of prism displacement on dynamic gait12

2006 ◽  
Vol 16 (1-2) ◽  
pp. 29-33
Author(s):  
Kim R. Gottshall ◽  
Michael E. Hoffer ◽  
Helen S. Cohen ◽  
Robert J. Moore
Keyword(s):  
Head Movement ◽  
Sensory Modality ◽  
Normal Subjects ◽  
The Body ◽  
Head Movements ◽  
Head Motion ◽  
Control Group ◽  
Entire Body ◽  
Group 3 ◽  
Group 2

Study design: Four groups, between-subjects study. Objectives: To investigate the effects of exercise on adaptation of normal subjects who had been artificially spatially disoriented. Background: Many patients referred for rehabilitation experience sensory changes, due to age or disease processes, and these changes affect motor skill. The best way to train patients to adapt to these changes and to improve their sensorimotor skills is unclear. Using normal subjects, we tested the hypothesis that active, planned head movement is needed to adapt to modified visual input. Methods and measures: Eighty male and female subjects who had normal balance on computerized dynamic posturography (CDP) and the dynamic gait index (DGI), were randomly assigned to four groups. All groups donned diagonally shift lenses and were again assessed with CDP and DGI. The four groups were then treated for 20 min. Group 1 (control group) viewed a video, Group 2 performed exercise that involved translating the entire body through space, but without separate, volitional head movement, Group 3 performed exercises which all incorporated volitional, planned head rotations, and Group 4 performed exercises that involved translating the body (as in Group 2) and incorporated volitional, planned head motion (as in Group 3). All subjects were post-tested with CDP and DGI, lenses were removed, and subjects were retested again with CDP and DGI. Results: The groups did not differ significantly on CDP scores but Groups 3 and 4 had significantly better DGI scores than Groups 1 and 2. Conclusions: Active head movement that is specifically planned as part of the exercise is more effective than passive attention or head movements that are not consciously planned, for adapting to sensorimotor change when it incorporates active use of the changed sensory modality, in this case head motion.

Evidence for the indirect utilization of glucose for the synthesis of hepatic glycogen in man

1992 ◽  
Vol 83 (6) ◽  
pp. 677-682
Author(s):  
R. F. G. J. King ◽  
M. Madan ◽  
D. Alexander ◽  
A. Boyd ◽  
K. Ibrahim ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Human Liver ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Indirect Pathway ◽  
Abdominal Operation ◽  
Direct Pathway ◽  
Specific Activities ◽  
Glycogen Repletion ◽  
Indirect Route

1. This study was designed to test the hypothesis that three-carbon intermediates can be used in the ‘indirect’ pathway of glycogen synthesis in human liver (i.e. a route additional to the use of glucose by the ‘direct’ pathway). 2. After an overnight fast, 13 patients were given an infusion of 20% (w/v) glucose before elective abdominal operation. All received a 2.5 g bolus of 2220 kBq of selectively 3H- and 14C-labelled glucose before removal of a 1 g biopsy of liver. 3H and 14C were determined in purified glycogen as well as in glucose and lactate from samples of peripheral blood. 3. The ratio and specific activities of 3H and 14C in glycogen were found to be significantly lower than those in administered glucose. By calculation, 7–74% of glycogen repletion occurred by indirect pathways and not all of this was from the glucose supplied. 4. This study suggests that the operation of a direct pathway in man is not exclusive and that significant repletion of hepatic glycogen occurs by an indirect route.

Hepatic glycogen accurately reflected by acetaminophen glucuronide in dogs refed after fasting

1995 ◽  
Vol 269 (4) ◽  
pp. E766-E773 ◽  
Author(s):  
K. I. Rother ◽  
W. F. Schwenk
Keyword(s):  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Indirect Pathway ◽  
Isotopic Tracers ◽  
Glucose Flux ◽  
Liver Biopsies ◽  
The Mean ◽  
Acetaminophen Glucuronide ◽  
Group 2

To validate a method to “biochemically biopsy” the immediate precursor of intrahepatic glycogen [uridyl diphosphate (UDP)-glucose] using acetaminophen and to assess how fasting affects the direct and indirect pathways of glycogen synthesis, dogs were fasted overnight (group 1, n = 5) or for 2.5 days (group 2, n = 5) and then given a 4-h duodenal infusion of unlabeled glucose, [3-3H]glucose, and [U-14C]lactate to label hepatic glycogen via the direct and indirect pathways, respectively, and [1-13C]galactose to measure intrahepatic UDP-glucose flux. After 3 h for equilibration, acetaminophen was given and urine was collected for acetaminophen glucuronide. Multiple liver biopsies were obtained. The mean 3H/14C ratios of glucose derived from glycogen (10.4 +/- 4.1 and 1.1 +/- 0.3 for groups 1 and 2, respectively) and glucose derived from acetaminophen glucuronide (11.5 +/- 4.0 and 1.0 +/- 0.1 for groups 1 and 2, respectively) were similar. Fasting significantly increased UDP-glucose flux, the rate of glycogen synthesis, and the contribution of the indirect pathway. We conclude that, in dogs, 1) no functional hepatic zonation exists with regard to acetaminophen glucuronidation and liver glycogen synthesis and 2) with appropriate choice of isotopic tracers and study design, UDP-glucose flux can accurately reflect rates of hepatic glycogen synthesis.

Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats

1985 ◽  
Vol 248 (5) ◽  
pp. E567-E574 ◽  
Author(s):  
D. E. James ◽  
A. B. Jenkins ◽  
E. W. Kraegen
Keyword(s):  
Insulin Sensitivity ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Relative Proportion ◽  
Glycogen Storage ◽  
Whole Body ◽  
Glucose Disposal ◽  
Maximal Effect ◽  
Euglycemic Hyperinsulinemic Clamp

The euglycemic hyperinsulinemic clamp technique in conscious unrestrained rats was used to examine the effect of insulin on glucose metabolism in metabolically distinct skeletal muscle in vivo. Tissue glucose metabolic rate (R'g) was estimated using 2-[3H]-deoxyglucose, and glucose disposal was examined by measuring glycogen content and [14C]glucose incorporation into glycogen in four different muscles. Insulin sensitivity varied among different muscle types in that the insulin concentration required for half-maximal stimulation of R'g was 80, 150, 280, and 320 mU/1 for soleus (SOL), red gastrocnemius (RG), white gastrocnemius (WG), and extensor digitorum longus, respectively. There were similar relative differences in the maximal effect of insulin on R'g in these muscles. Maximal insulin stimulation almost doubled muscle glycogen content in RG and SOL, whereas there was no change in WG. The relationship between R'g and glycogen synthesis indicated that increased glucose uptake resulted predominantly in glycogen storage. There was an excellent relationship between maximal R'g and blood flow in different muscles. We conclude that there is marked heterogeneity in insulin sensitivity and responsiveness among muscles of different fiber composition. Insulin-induced increases in total peripheral glucose disposal occur predominantly in muscles containing a high proportion of oxidative fibers. Therefore the relative proportion of oxidative to glycolytic muscle fibers may be important factors in determining whole body insulin sensitivity.

Effects of physiological hyperinsulinemia on the intracellular metabolic partition of plasma glucose

1993 ◽  
Vol 265 (6) ◽  
pp. E943-E953 ◽  
Author(s):  
R. C. Bonadonna ◽  
S. del Prato ◽  
E. Bonora ◽  
G. Gulli ◽  
A. Solini ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Healthy Subjects ◽  
Glucose Oxidation ◽  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Glucose Infusion ◽  
Glucose Disposal ◽  
Hepatic Glucose ◽  
Glucose Recycling

Methodology for assessing the glycolytic and oxidative fluxes from plasma glucose, by measuring 3H2O and 14CO2 rates of production during [3-3H]- and [U-14C]glucose infusion, was tested in healthy subjects. In study 1, during staircase 3H2O infusion in six subjects, calculated rates of 3H2O appearance agreed closely with 3H2O infusion rates. In study 2, when [2-3H]glucose and NaH14CO3 were infused in four subjects in the basal state and during a 4-h euglycemic insulin (approximately 70 microU/ml) clamp, accurate estimates of the rates of [2-3H]glucose detritiation were obtained (94-97% of the expected values), and the recovery factor of NaH14CO3 did not change during hyperinsulinemia. In study 3, 11 subjects underwent a 4-h euglycemic insulin (approximately 70 microU/ml) clamp with [3-3H]- and [U-14C]glucose infusion and measurement of gaseous exchanges by indirect calorimetry to estimate the rates of total glycolysis, glycogen synthesis, glucose oxidation, nonoxidative glycolysis, hepatic glucose production, glucose recycling, and glucose conversion to fat. Hyperinsulinemia stimulated glycogen synthesis above baseline more than glycolysis [increment of 4.78 +/- 0.37 vs. 2.0 +/- 0.17 mg.min-1 x kg-1 of lean body mass (LBM), respectively, P < 0.01] and incompletely suppressed (approximately 87%) hepatic glucose production. The major component of nonoxidative glycolysis shifted from glucose recycling in the postabsorptive state (approximately 57% of nonoxidative glycolysis) to glucose conversion to fat during hyperinsulinemia (approximately 59% of nonoxidative glycolysis). Lipid oxidation during the insulin clamp was negatively correlated with both isotopic glucose oxidation (r = -0.822, P < 0.002) and glycolysis (r = -0.582, P < 0.07). In conclusion, in healthy subjects, glycogen synthesis plays a greater role than glycolysis and glucose oxidation in determining insulin-mediated glucose disposal. Part of insulin-mediated increase in glycolysis/oxidation might be secondary to the relief of the competition between fat and glucose for oxidation.

Postoperative Dysphagia versus Neurogenic Dysphagia: Scintigraphic Assessment

2003 ◽  
Vol 112 (1) ◽  
pp. 20-28 ◽  
Author(s):  
Venanzio Valenza ◽  
AnaMaria Samanes Gajate ◽  
Jacopo Galli ◽  
Lucia D'Alatri ◽  
Stefano Di Girolamo ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Transit Time ◽  
Retention Index ◽  
Normal Subjects ◽  
Mean Value ◽  
Esophageal Transit ◽  
Maximum Value ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

In order to differentiate the features of dysphagia that occur after supraglottic horizontal laryngectomy from those that occur during neurologic diseases, we divided 38 subjects into 3 groups and submitted them to oropharyngoesophageal scintigraphy. Group 1 (control group) included 15 healthy volunteeers; group 2 comprised 8 patients who had residual dysphagia at least 1 year after supraglottic laryngectomy; and group 3 included 15 patients with various neurologic and neuromuscular disorders. In group 1, the mean values (±2 SD) of selected semiquantitative parameters were consistent with those reported in the literature for normal subjects. In group 2, oral, pharyngeal, and esophageal transit times were not significantly altered, and moderate tracheobronchial postdeglutitive aspiration was present (maximum value, 6.7%; mean value, 2.04%). The pharyngeal retention index was significantly increased (p = .0003) as compared to normal subjects in all cases (maximum value, 40%; mean value, 23%) and was associated in all cases with slight but consistent postdeglutitive aspiration. In group 3, the oral and esophageal phases were significantly prolonged and the retention indices were significantly increased. Statistical analysis documented a significant increase in oral transit time (p = .003), esophageal transit time (p = .01), oral retention index (p = .006), pharyngeal retention index (p = .0007), and esophageal retention index (p = .009) as compared to normal subjects. The swallowing pattern was also altered by 1) an early loss of the bolus from the oral cavity; 2) bolus fragmentation due to double or triple deglutition, reduced lingual propulsion, or the return of a small part of the bolus into the oral cavity during deglutition; and/or 3) double pharyngeal peaks in the activity-time curves. Tracheobronchial aspiration (maximum value, 90%; mean value, 9.70%) was present in some cases, mainly in patients affected by post-stroke dysphagia. On the basis of the obtained results and considering the low doses of radiation delivered to the patient (0.043 Gy), the limited invasiveness, and the excellent patient tolerance, scintigraphy appears to be clinically valid in the functional study of swallowing and in identifying different deglutition disorders.

Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration

2012 ◽  
Vol 303 (7) ◽  
pp. E875-E885 ◽  
Author(s):  
Ana F. Soares ◽  
Rui A. Carvalho ◽  
Francisco J. Veiga ◽  
Marco G. Alves ◽  
Fátima O. Martins ◽  
...  
Keyword(s):  
De Novo ◽  
Glycogen Synthesis ◽  
Insulin Dependent Diabetes ◽  
De Novo Lipogenesis ◽  
Hepatic Glycogen ◽  
Insulin Administration ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Nocturnal Feeding ◽  
Insulin Dependent

Type 1 diabetes subjects are characterized by impaired direct pathway synthesis of hepatic glycogen that is unresponsive to insulin therapy. Since it is not known whether this is an irreversible defect of insulin-dependent diabetes, direct and indirect pathway glycogen fluxes were quantified in streptozotocin (STZ)-induced diabetic rats and compared with STZ rats that received subcutaneous or intraperitoneal insulin (I-SC or I-IP). Three groups of STZ rats were studied at 18 days post-STZ treatment. One group was administered I-SC and another I-IP as two daily injections of short-acting insulin at the start of each light and dark period for days 9–18. A third group did not receive any insulin, and a fourth group of nondiabetic rats was used as control. Glycogen synthesis via direct and indirect pathways, de novo lipogenesis, and gluconeogenesis were determined over the nocturnal feeding period using deuterated water. Direct pathway was residual in STZ rats, and glucokinase activity was also reduced significantly from control levels. Insulin administration restored both net glycogen synthesis via the direct pathway and glucokinase activity to nondiabetic control levels and improved the lipogenic pathway despite an inefficient normalization of the gluconeogenic pathway. We conclude that the reduced direct pathway flux is not an irreversible defect of insulin-dependent diabetes.

scholarly journals Glucose autoregulation is the dominant component of the hormone-independent counterregulatory response to hypoglycemia in the conscious dog

2017 ◽  
Vol 313 (3) ◽  
pp. E273-E283 ◽  
Author(s):  
Justin M. Gregory ◽  
Noelia Rivera ◽  
Guillaume Kraft ◽  
Jason J. Winnick ◽  
Ben Farmer ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Muscle Group ◽  
The Body ◽  
Hepatic Glycogen ◽  
Hepatic Glucose ◽  
Group 3 ◽  
Per Se ◽  
Group 2 ◽  
Group 1

The contribution of hormone-independent counterregulatory signals in defense of insulin-induced hypoglycemia was determined in adrenalectomized, overnight-fasted conscious dogs receiving hepatic portal vein insulin infusions at a rate 20-fold basal. Either euglycemia was maintained ( group 1) or hypoglycemia (≈45 mg/dl) was allowed to occur. There were three hypoglycemic groups: one in which hepatic autoregulation against hypoglycemia occurred in the absence of sympathetic nervous system input ( group 2), one in which autoregulation occurred in the presence of norepinephrine (NE) signaling to fat and muscle ( group 3), and one in which autoregulation occurred in the presence of NE signaling to fat, muscle, and liver ( group 4). Average net hepatic glucose balance (NHGB) during the last hour for groups 1–4 was −0.7 ± 0.1, 0.3 ± 0.1 ( P < 0.01 vs. group 1), 0.7 ± 0.1 ( P = 0.01 vs. group 2), and 0.8 ± 0.1 ( P = 0.7 vs. group 3) mg·kg−1·min−1, respectively. Hypoglycemia per se ( group 2) increased NHGB by causing an inhibition of net hepatic glycogen synthesis. NE signaling to fat and muscle ( group 3) increased NHGB further by mobilizing gluconeogenic precursors resulting in a rise in gluconeogenesis. Lowering glucose per se decreased nonhepatic glucose uptake by 8.9 mg·kg−1·min−1, and the addition of increased neural efferent signaling to muscle and fat blocked glucose uptake further by 3.2 mg·kg−1·min−1. The addition of increased neural efferent input to liver did not affect NHGB or nonhepatic glucose uptake significantly. In conclusion, even in the absence of increases in counterregulatory hormones, the body can defend itself against hypoglycemia using glucose autoregulation and increased neural efferent signaling, both of which stimulate hepatic glucose production and limit glucose utilization.

Exercise and exhaustion effects on glycogen synthesis pathways

1996 ◽  
Vol 81 (5) ◽  
pp. 2020-2026 ◽  
Author(s):  
Hans Gunderson ◽  
Nadja Wehmeyer ◽  
Diane Burnett ◽  
John Nauman ◽  
Cynthia Hartzell ◽  
...  
Keyword(s):  
Endurance Training ◽  
Glycogen Synthesis ◽  
Exhaustive Exercise ◽  
Hepatic Glycogen ◽  
Sprague Dawley ◽  
Indirect Pathway ◽  
Comparable Amount ◽  
Direct Pathway ◽  
Metabolic States ◽  
Metabolic Conditions

Gunderson, Hans, Nadja Wehmeyer, Diane Burnett, John Nauman, Cynthia Hartzell, and Scott Savage. Exercise and exhaustion effects on glycogen synthesis pathways. J. Appl. Physiol. 81(5): 2020–2026, 1996.—Female Sprague-Dawley rats were infused with [1-13C]glucose to measure the effect of endurance training and the effect of various metabolic conditions on pathways of hepatic glycogen synthesis. Four metabolic states [sedentary (S), trained (T), sedentary exhausted (SE), and trained exhausted (TE)] were studied. T and TE rats were trained on a motor-driven treadmill (30 m/min, 15% grade, 1.0 h/day, 5 days/wk) for 8–10 wk. After a 24-h fast, SE and TE rats were run to exhaustion (sedentary average = 78 min, trained average = 155 min) at a training pace and immediately infused with labeled glucose for 2 h. S and T rats were infused after a 24-h fast. After infusion, tissues were removed and glycogen was isolated and hydrolyzed to glucose. The glucose was measured for distribution of13C by using nuclear magnetic resonance. Glycogen was synthesized predominantly by the indirect pathway for all metabolic states, indicating that infused glucose was first metabolized primarily in the peripheral tissue. The direct-pathway utilization was greater in rested S than in rested T animals (30 vs. 14%); however, for exhausted animals, the trained use of the direct pathway was greater (22 vs. 9%). Both TE and rested T animals utilize the indirect pathway a comparable amount. Sedentary animals, on the other hand, dramatically decreased utilization of the direct pathway, with exhaustive exercise changing from 30 to 9%. The results indicate that endurance training modifies glucose utilization during glycogen synthesis after fasting and exhaustive exercise.

Gluconeogenic pathway in liver and muscle glycogen synthesis after exercise

1988 ◽  
Vol 64 (4) ◽  
pp. 1591-1599 ◽  
Author(s):  
J. L. Johnson ◽  
G. J. Bagby
Keyword(s):  
Plasma Glucose ◽  
Muscle Glycogen ◽  
White Muscle ◽  
Glycogen Synthesis ◽  
Plasma Lactate ◽  
Indirect Pathway ◽  
Direct Pathway ◽  
Prior Exercise ◽  
Muscle Glycogen Synthesis ◽  
Lactate Levels

To determine whether prior exercise affects the pathways of liver and muscle glycogen synthesis, rested and postexercised rats fasted for 24 h were infused with glucose (200 mumol.min-1.kg-1 iv) containing [6-3H]glucose. Hyperglycemia was exaggerated in postexercised rats, but blood lactate levels were lower than in nonexercised rats. The percent of hepatic glycogen synthesized from the indirect pathway (via gluconeogenesis) did not differ between exercised (39%) and nonexercised (36%) rats. In red muscle, glycogen was synthesized entirely by the direct pathway (uptake and phosphorylation of plasma glucose) in both groups. However, only approximately 50% of glycogen was formed via the direct pathway in white muscle of exercised and nonexercised rats. Therefore prior exercise did not alter the pathways of tissue glycogen synthesis. To further study the incorporation of gluconeogenic precursors into muscle glycogen, exercised rats were infused with either saline, lactate (100 mumol.min-1.kg-1), or glucose (200 mumol.min-1.kg-1), containing [6-3H]glucose and [14C(U)]lactate. Plasma glucose was elevated one- to twofold and three- to fourfold by lactate and glucose infusion, respectively. Plasma lactate levels were elevated by about threefold during both glucose and lactate infusion. Glycogen was partially synthesized via an indirect pathway in white muscle and liver of glucose- or lactate-infused rats but not in saline-infused animals. Thus participation of an indirect pathway in white skeletal muscle glycogen synthesis required prolonged elevation of plasma lactate levels produced by nutritive support.

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