Muscle glycogen synthesis and breakdown are both impaired in glycogenin-1 deficiency

Neurology ◽  
2017 ◽  
Vol 89 (24) ◽  
pp. 2491-2494 ◽  
Author(s):  
Mads Godtfeldt Stemmerik ◽  
Karen Lindhardt Madsen ◽  
Pascal Laforêt ◽  
Astrid Emilie Buch ◽  
John Vissing
Keyword(s):  
Heart Rate ◽  
Exercise Tolerance ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Glucose Infusion ◽  
Exercise Intolerance ◽  
Muscle Glycogen Synthesis ◽  
Workload Capacity ◽  
Isotope Technique ◽  
Exercise Induced

Objective:To study fat and carbohydrate metabolism during exercise in patients with glycogenin-1 (GYG1) deficiency, and to study whether IV glucose supplementation can alleviate exercise intolerance in these patients.Methods:This is a case-control study with 4 patients with GYG1 deficiency and 4 healthy controls. Patients performed 1 hour of cycling at 50% of their maximal workload capacity, while controls cycled at the same absolute workloads as patients. Heart rate was measured continuously, and production and utilization of fat and glucose was assessed by stable isotope technique. The following day, patients repeated the exercise, this time receiving an IV 10% glucose supplement.Results:Glucose utilization during exercise was similar in patients and controls, while palmitate utilization was greater in patients compared to controls. However, exercise-induced increases in lactate were attenuated to about half normal in patients. This was also the case during a handgrip exercise test. Glucose infusion improved exercise tolerance in patients, and lowered heart rate by on average 11 beats per minute during exercise.Conclusions:The findings suggest that patients with GYG1 deficiency not only have abnormal formation of glycogen, but also have impaired muscle glycogenolysis, as suggested by impaired lactate production during exercise and improved exercise tolerance with glucose infusion.

Effects of FFA on insulin-stimulated glucose fluxes and muscle glycogen synthase activity in rats

1998 ◽  
Vol 275 (2) ◽  
pp. E338-E344 ◽  
Author(s):  
Joong-Yeol Park ◽  
Chul-Hee Kim ◽  
Sung K. Hong ◽  
Kyo I. Suh ◽  
Ki-Up Lee
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Infusion Rate ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Whole Body ◽  
Heparin Infusion ◽  
Muscle Glycogen Synthesis

To examine effects of free fatty acids (FFA) on insulin-stimulated glucose fluxes, euglycemic hyperinsulinemic (86 pmol ⋅ kg−1 ⋅ min−1) clamps were performed for 5 h in conscious rats with ( n = 8) or without ( n = 8) lipid-heparin infusion. Glucose infusion rate required to maintain euglycemia was not different between the two groups during the first 2 h of clamps but became significantly lower with lipid-heparin infusion in the 3rd h and thereafter. To investigate changes in intracellular glucose metabolism during lipid-heparin infusion, additional clamps ( n = 8 each) were performed for 1, 2, 3, or 5 h with an infusion of [3-3H]glucose. Insulin-stimulated whole body glucose utilization (Rd), glycolysis, and glycogen synthesis were estimated on the basis of tracer concentrations in plasma during the final 40 min of each clamp. Similar to changes in glucose infusion rate, Rd was not different between the two groups in the 1st and 2nd h but was significantly lower with lipid-heparin infusion in the 3rd h and thereafter. Whole body glycolysis was significantly lower with lipid-heparin infusion in all time periods, i.e., 1st, 2nd, 3rd, and 5th h of clamps. In contrast, whole body glycogen synthesis was higher with lipid-heparin infusion in the 1st and 2nd h but lower in the 5th h. Similarly, accumulation of [3H]glycogen radioactivity in muscle glycogen was significantly higher with lipid-heparin during the 1st and 2nd h but lower during the 3rd and 5th h. Glucose 6-phosphate (G-6- P) concentrations in gastrocnemius muscles were significantly higher with lipid-heparin infusion throughout the clamps. Muscle glycogen synthase (GS) activity was not altered with lipid-heparin infusion at 1, 2, and 3 h but was significantly lower at 5 h. Thus increased availability of FFA significantly reduced whole body glycolysis, but compensatory increase in skeletal muscle glycogen synthesis in association with accumulation of G-6- P masked this effect, and Rd was not affected in the early phase (within 2 h) of lipid-heparin infusion. Rd was reduced in the later phase (>2 h) of lipid-heparin infusion, when glycogen synthesis was reduced in association with reduced skeletal muscle GS activity.

scholarly journals Relationship between blood pressure response during hemodialysis and exercise tolerance or heart rate recovery measured using cardio-pulmonary exercise testing in maintenance hemodialysis patients

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Hiroki Yabe ◽  
Kenichi Kono ◽  
Ryota Shiraki ◽  
Akiho Masuda ◽  
Yoshifumi Moriyama ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Oxygen Uptake ◽  
Exercise Testing ◽  
Exercise Tolerance ◽  
Blood Pressure Response ◽  
Heart Rate Recovery ◽  
Cardiopulmonary Exercise Testing ◽  
Pressure Response ◽  
Exercise Intolerance

Abstract Background This study investigated the association between the blood pressure response during hemodialysis (HD) and exercise tolerance or heart rate recovery (HRR) measured with cardiopulmonary exercise testing (CPX). Methods The study enrolled 23 patients who had been undergoing 4-h regular maintenance HD. The maximum workload (Loadpeak), peak oxygen uptake (VO2peak), workload and oxygen uptake at the anaerobic threshold (LoadAT and VO2AT, respectively), and HRR were measured with CPX. The average systolic blood pressure during HD (SBPav) was measured, and the number of times the SBP was less than 100 mmHg was determined in the 2-week period after CPX. Results The SBPav showed a significant correlation with LoadAT (r = 0.46) and Loadpeak (r = 0.43, p < 0.05). The number of times the SBP was less than 100 mmHg showed a significant correlation with the HRR (r = − 0.44, p < 0.05). Conclusion Exercise intolerance and HRR in HD patients may be associated with blood pressure instability during HD.

Effect of hepatic nerves on disposition of an intraduodenal glucose load

1993 ◽  
Vol 265 (3) ◽  
pp. E487-E496 ◽  
Author(s):  
M. C. Moore ◽  
G. I. Shulman ◽  
A. Giaccari ◽  
M. J. Pagliassotti ◽  
G. Cline ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Glucose Infusion ◽  
Hepatic Glycogen ◽  
Indirect Pathway ◽  
Hepatic Glucose ◽  
Hepatic Glucose Uptake ◽  
Hepatic Nerves ◽  
Glycogen Synthase Activity

We examined the disposition of a continuous 4-h intraduodenal glucose infusion (8 mg.kg-1 x min-1, labeled with [1-13C]glucose and [3-3H]glucose) in nine conscious hepatic-denervated dogs. Cumulative net hepatic uptakes (in grams of glucose equivalents) were 13.7 +/- 2.5 glucose, 3.1 +/- 0.6 gluconeogenic amino acids, and 0.8 +/- 0.1 glycerol. Net hepatic glycogen synthesis totalled 11.0 +/- 0.9 g, 55-62% via the direct pathway. All values were similar to those in hepatic-innervated dogs. Glycogen synthase activity and rate of glycogen synthesis were positively correlated (r2 = 0.913, P < 0.05). Variability in net hepatic glycogen synthesis and the mass of glycogen synthesized via the indirect pathway was reduced in hepatic-denervated dogs (P < 0.05). In conclusion, the glycemic response and rate of net glycogen synthesis during an intraduodenal glucose infusion was no different in hepatic-denervated and -innervated dogs. Net hepatic glucose uptake was sufficient to account for all net hepatic glycogen synthesis and lactate production, consistent with an intrahepatic source of gluconeogenic precursors for glycogen synthesis via the indirect pathway. Hepatic nerves appear responsible for much of the variability in net hepatic glycogen synthesis and in the mass of glycogen synthesized via the indirect pathway in normal dogs.

scholarly journals Exercise Intolerance and Oxygen Desaturation in Patients with Parkinson’s Disease: Triggers for Respiratory Rehabilitation?

2021 ◽  
Vol 18 (23) ◽  
pp. 12298
Author(s):  
Michele Vitacca ◽  
Adriana Olivares ◽  
Laura Comini ◽  
Giuliana Vezzadini ◽  
Annamaria Langella ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Function ◽  
Exercise Tolerance ◽  
Respiratory Muscles ◽  
Functional Independence ◽  
Oxygen Desaturation ◽  
Exercise Intolerance ◽  
Exercise Induced ◽  
Respiratory Rehabilitation

The role that oxygen desaturation plays in exercise tolerance and its rehabilitative implications in patients with Parkinson’s disease (PD) are unclear. We aimed to test exercise tolerance and oxygen saturation levels both during exercise and at night in PD patients to better define their rehabilitative needs. In clinically stable PD patients, undergoing inpatient rehabilitation, and in “ON” phase, we prospectively assessed clinical data, sleepiness, comorbidities, PD severity (Hoehn&Yahr, HY), motor function (ADLs, UPDRSII and UPDRSIII, Barthel Index, Functional Independence Measure), balance, spirometry, respiratory muscles (MIP/MEP), peak cough expiratory flow (PCEF), continuous night oxygen monitoring, and meters at 6MWD. Of 55 patients analyzed (28 with moderate–severe PD, HY ≥ 2.5), 37% and 23% showed moderate–severe impairment on UPDRSII and UPDRSIII, respectively; 96% had reduced exercise tolerance and severe respiratory muscles impairment (MIP/MEP < 45%pred.); 21.8% showed desaturations during exercise; and 12.7% showed nocturnal desaturations. At multiple regression, low exercise tolerance and low mean nocturnal and exercise-induced saturation correlated with several respiratory and motor function and disability indices (all p < 0.03). Exercise tolerance, exercise-induced desaturations, and nocturnal desaturations were extremely frequent in PD patients and were worse in more severe PD patients. This suggests considering a combined role for motor and respiratory rehabilitation in these patients.

ÉTUDE IN VITRO DU MÉTABOLISME DES HYDRATES DE CARBONE DANS LE LEUCOCYTE CIRCULANT DU COBAYE TRAITÉ À LA CORTISONE

1966 ◽  
Vol 51 (2) ◽  
pp. 193-202
Author(s):  
J. A. Antonioli ◽  
A. Vannotti
Keyword(s):  
Glucose Concentration ◽  
Intramuscular Injection ◽  
Acute Inflammation ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
List Type ◽  
Hydrates De Carbone

ABSTRACT 1. The metabolism of suspensions of circulating leucocytes has been studied after intramuscular injection of a dose of 50 mg/kg of a corticosteroid (cortisone acetate). The suspensions were incubated under aerobic conditions in the presence of a glucose concentration of 5.6 mm. Glucose consumption, lactate production, and variations in intracellular glycogen concentration were measured. After the administration of the corticosteroid, the anabolic processes of granulocyte metabolism were reversibly stimulated. Glucose consumption and lactate production increased 12 hours after the injection, but tended to normalize after 24 hours. The glycogen content of the granulocytes was enhanced, and glycogen synthesis during the course of the incubation was greatly stimulated. The action of the administered corticosteroid is more prolonged in females than in males. The injection of the corticosteroid caused metabolic modifications which resemble in their modulations and in their chronological development those found in circulating granulocytes of guinea-pigs suffering from sterile peritonitis. These results suggest, therefore, that, in the case of acute inflammation, the glucocorticosteroids may play an important role in the regulation of the metabolism of the blood leucocytes.

scholarly journals The effectiveness of supplemental oxygen during exercise training in patients with chronic obstructive pulmonary disease who show severe exercise-induced desaturation: a protocol for a meta-regression analysis and systematic review

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Shohei Kawachi ◽  
Shuhei Yamamoto ◽  
Kenichi Nishie ◽  
Takayoshi Yamaga ◽  
Manaka Shibuya ◽  
...  
Keyword(s):  
Systematic Review ◽  
Exercise Training ◽  
Exercise Tolerance ◽  
Supplemental Oxygen ◽  
Walking Distance ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Severe Exercise ◽  
Meta Regression ◽  
Exercise Induced

Abstract Background Supplemental oxygen during exercise training is used to increase the training effect of an exercise program in patients with chronic obstructive pulmonary disease (COPD) who show exercise-induced desaturation. Exercise-induced desaturation is not clearly defined in the guidelines; however, it is generally defined in clinical studies as a decrease in SpO2 of more than 4% from rest or a decrease to less than 88% during exercise. Although some meta-analyses examined the effectiveness of supplemental oxygen during exercise training, these studies concluded that it does not further improve exercise tolerance compared to exercise training alone. However, supplemental oxygen during exercise training may be effective in improving exercise tolerance in COPD patients with severe exercise-induced desaturation. Therefore, this study will be performed to elucidate the effectiveness of supplemental oxygen during exercise training and the relationship between its effectiveness and severity of exercise-induced desaturation at baseline. Methods We will first assess the effectiveness of supplemental oxygen during exercise training in COPD. The main outcome is the change in exercise tolerance before and after the intervention, indicated by the 6-min walking distance, the walking distance, or the walking time in incremental shuttle walking test, and analyzed as the standardized mean difference (SMD). The quality and risk of bias in individual studies will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and risk-of-bias tool (RoB ver.2). If statistical heterogeneity in terms of the effectiveness of exercise tolerance is shown, we will conduct meta-regression analyses to examine the association between the effectiveness of exercise training with supplemental oxygen and severity of exercise-induced desaturation at baseline. Discussion One strength of this study is that it is a systematic review with meta-regression analysis to elucidate the effectiveness of supplemental oxygen during exercise training in patients with COPD who show severe exercise-induced desaturation. Furthermore, we will assess the severity of exercise-induced desaturation for which exercise training with supplemental oxygen is effective, the influence of acute effects at baseline, and the effect of supplemental oxygen on adverse events. Systematic review registration Registration number, UMIN000039960.

scholarly journals β1-blocker in sepsis

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Daisuke Hasegawa ◽  
Ryota Sato ◽  
Osamu Nishida
Keyword(s):  
Heart Rate ◽  
Oxygen Delivery ◽  
Sinus Tachycardia ◽  
Meta Analysis ◽  
Lactate Production ◽  
Volume Index ◽  
Initial Resuscitation ◽  
Randomized Controlled ◽  
Metabolic Systems

Abstract Background The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical evidence of ultrashort-acting β1-blockers. Main body A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation. Conclusion Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted.

Is there an exercise duration threshold for exercise-induced troponin elevation in healthy recreational athletes? The NEEDED 2014 advanced heart rate monitor substudy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Bjorkavoll-Bergseth ◽  
B Auestad ◽  
O Kleiven ◽  
O Skadberg ◽  
T Eftestol ◽  
...  
Keyword(s):  
Heart Rate ◽  
Clinical Status ◽  
Exercise Duration ◽  
Strenuous Exercise ◽  
Clinical Consequence ◽  
Funding Source ◽  
Recreational Athletes ◽  
National Budget ◽  
Exercise Induced ◽  
Public Grant

Abstract Background/Introduction Following prolonged strenuous exercise there is an exercise-induced troponin (cTn) elevation in healthy individuals. The precise mechanisms and clinical consequence of this cTn elevation remain to be determined. It has recently been demonstrated that exercise intensity, exceeding a heart rate (HR) of 150 bpm, is correlated with exercise-induced cTn elevation. Purpose The present work aims to determine if there is a threshold for exercise duration with a HR exceeding 150 bpm associated with an excessive exercise-induced cTn elevation. Methods A total of 177 healthy subjects were included in the present analysis of HR data obtained from sport watches used during a 91-km recreational mountain bike cycle race. Clinical status, cTnI, ECGs, blood pressure and demographics were obtained 24 h prior to- and at 3 h and 24 h after the race. Results are reported as median and 25th and 75th percentile. We used Tree regression to determine the association between elevated cTnI and exercise duration exceeding a HR of 150 bpm. Results Subjects were 82% (n=146) males, 44 (39–51) years, with a race time of 3.5 (3.1–3.9) h. Baseline cTnI was 1.9 (1.6–3.3) ng/L. There was a cTnI elevation in all study participants at 3 h, cTnI: 60.0 (36.0–99.3) ng/L, with a significant (p&lt;0.001) reduction at 24 hours following exercise, cTnI: 10.9 (6.1–22.4) ng/L. Tree regression identified 168 min of exercise, with a HR exceeding 150 bpm, to be associated with an excessive increase in cTnI both at 3 h, and at 24 h following the race (figure). The median cTn values above and below the threshold are presented in the Table. Conclusion The present analysis suggests that exceeding a specific duration of high intensity exercise may be associated with excessive cTn elevation in susceptible individuals. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Western Norway Health authoritites.

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