Carbohydrate metabolism in fructose-fed and food-restricted running rats

1986 ◽  
Vol 61 (4) ◽  
pp. 1457-1466 ◽  
Author(s):  
B. Sonne ◽  
H. Galbo
Keyword(s):  
Carbohydrate Metabolism ◽  
Plasma Glucose ◽  
Direct Synthesis ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Treadmill Running ◽  
Hepatic Glycogen ◽  
Work Intensity ◽  
Glycogen Breakdown

In chronically catheterized rats hepatic glycogen was increased by fructose (approximately 10 g/kg) gavage (FF rats) or lowered by overnight food restriction (FR rats). [3-3H]- and [U-14C]glucose were infused before, during, and after treadmill running. During exercise the increase in glucose production (Ra) was always directly related to work intensity and faster than the increase in glucose disappearance, resulting in increased plasma glucose levels. At identical work-loads the increase in Ra and plasma glucose as well as liver glycogen breakdown were higher in FF and control (C) rats than in FR rats. Breakdown of muscle glycogen was less in FF than in C rats. Incorporation of [14C]glucose in glycogen at rest and mobilization of label during exercise partly explained that 14C estimates of carbohydrate metabolism disagreed with chemical measurements. In some muscles glycogen depletion was not accompanied by loss of 14C and 3H, indicating futile cycling of glucose. In FR rats a postexercise increase in liver glycogen was seen with 14C/3H similar to that of plasma glucose, indicating direct synthesis from glucose. In conclusion, in exercising rats the increase in glucose production is subjected to feedforward regulation and depends on the liver glycogen concentration. Endogenous glucose may be incorporated in glycogen in working muscle and may be used directly for liver glycogen synthesis rather than after conversion to trioses. Fructose ingestion may diminish muscular glycogen breakdown. The [14C]glucose infusion technique for determination of muscular glycogenolysis is of doubtful value in rats.

Effect of liver glycogen content on glucose production in running rats

1989 ◽  
Vol 66 (1) ◽  
pp. 318-322 ◽  
Author(s):  
J. Vissing ◽  
J. L. Wallace ◽  
H. Galbo
Keyword(s):  
Plasma Glucose ◽  
Glycogen Content ◽  
Hepatic Glucose Production ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Treadmill Running ◽  
Hepatic Glycogen ◽  
Hepatic Glucose ◽  
Exercise Induced

The influence of supranormal compared with normal hepatic glycogen levels on hepatic glucose production (Ra) during exercise was investigated in chronically catheterized rats. Supranormal hepatic glycogen levels were obtained by a 24-h fast-24-h refeeding regimen. During treadmill running for 35 min at a speed of 21 m/min, Ra and plasma glucose increased more (P less than 0.05) and liver glucogen breakdown was larger in fasted-refed compared with control rats, although the stimuli for Ra were higher in control rats, the plasma concentrations of insulin and glucose being lower (P less than 0.05) in control compared with fasted-refed rats. Also, plasma concentrations of glucagon and both catecholamines tended to be higher and muscle glycogenolysis lower in control compared with fasted-refed rats. Lipid metabolism was similar in the two groups. The results indicate that hepatic glycogenolysis during exercise is directly related to hepatic glycogen content. The smaller endocrine glycogenolytic signal in face of higher plasma glucose concentrations in fasted-refed compared with control rats is indicative of metabolic feedback control of glucose mobilization during exercise. However, the higher exercise-induced increase in Ra, plasma glucose, and liver glycogen breakdown in fasted-refed compared with control rats indicates that metabolic feedback mechanisms are not able to accurately match Ra to the metabolic needs of working muscles.

Plasma glucose concentration determines direct versus indirect liver glycogen synthesis

1986 ◽  
Vol 251 (5) ◽  
pp. E584-E590 ◽  
Author(s):  
C. H. Lang ◽  
G. J. Bagby ◽  
H. L. Blakesley ◽  
J. L. Johnson ◽  
J. J. Spitzer
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Infusion Rate ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Hepatic Glycogen ◽  
Glucose Load ◽  
Indirect Pathway

In the present study hepatic glycogenesis by the direct versus indirect pathway was determined as a function of the glucose infusion rate. Glycogen synthesis was examined in catheterized conscious rats that had been fasted 48 h before receiving a 3-h infusion (iv) of glucose. Glucose, containing tracer quantities of [U-14C]- and [6-3H]glucose, was infused at rates ranging from 0 to 230 mumol X min-1 X kg-1. Plasma concentrations of glucose, lactate, and insulin were positively correlated with the glucose infusion rate. Despite large changes in plasma glucose, lactate, and insulin concentrations, the rate of hepatic glycogen deposition (0.46 +/- 0.03 mumol X min-1 X g-1) did not vary significantly between glucose infusion rates of 20 and 230 mumol X min-1 X kg-1. However, the percent contribution of the direct pathway to glycogen repletion gradually increased from 13 +/- 2 to 74 +/- 4% in the lowest to the highest glucose infusion rates, with prevailing plasma glucose concentrations from 9.4 +/- 0.5 to 21.5 +/- 2.1 mM. Endogenous glucose production was depressed (by up to 40%), but not abolished by the glucose infusions. Only a small fraction (7-14%) of the infused glucose load was incorporated into liver glycogen via the direct pathway irrespective of the glucose infusion rate. Our data indicate that the relative contribution of the direct and indirect pathways of hepatic glycogen synthesis are dependent on the glucose load or plasma glucose concentration and emphasize the predominance of the indirect pathway of glycogenesis at plasma glucose concentrations normally observed after feeding.

scholarly journals Is Insulin Action in the Brain Relevant in Regulating Blood Glucose in Humans?

2015 ◽  
Vol 100 (7) ◽  
pp. 2525-2531 ◽  
Author(s):  
Satya Dash ◽  
Changting Xiao ◽  
Cecilia Morgantini ◽  
Khajag Koulajian ◽  
Gary F. Lewis
Keyword(s):  
Plasma Glucose ◽  
Insulin Action ◽  
Hepatic Glucose Production ◽  
Glycogen Synthesis ◽  
Physiological Role ◽  
Glucose Production ◽  
Insulin Concentration ◽  
Hepatic Glycogen ◽  
Hepatic Glucose ◽  
Glucose Output

Purpose: In addition to its direct action on the liver to lower hepatic glucose production, insulin action in the central nervous system (CNS) also lowers hepatic glucose production in rodents after 4 hours. Although CNS insulin action (CNSIA) modulates hepatic glycogen synthesis in dogs, it has no net effect on hepatic glucose output over a 4-hour period. The role of CNSIA in regulating plasma glucose has recently been examined in humans and is the focus of this review. Methods and Results: Intransal insulin (INI) administration increases CNS insulin concentration. Hence, INI can address whether CNSIA regulates plasma glucose concentration in humans. We and three other groups have sought to answer this question, with differing conclusions. Here we will review the critical aspects of each study, including its design, which may explain these discordant conclusions. Conclusions: The early glucose-lowering effect of INI is likely due to spillover of insulin into the systemic circulation. In the presence of simultaneous portal and CNS hyperinsulinemia, portal insulin action is dominant. INI administration does lower plasma glucose independent of peripheral insulin concentration (between ∼3 and 6 h after administration), suggesting that CNSIA may play a role in glucose homeostasis in the late postprandial period when its action is likely greatest and portal insulin concentration is at baseline. The potential physiological role and purpose of this pathway are discussed in this review. Because the effects of INI are attenuated in patients with type 2 diabetes and obesity, this is unlikely to be of therapeutic utility.

Glucose production in glycogen storage disease I is not associated with increased cycling through hepatic glycogen

1995 ◽  
Vol 269 (4) ◽  
pp. E774-E778 ◽  
Author(s):  
K. I. Rother ◽  
W. F. Schwenk
Keyword(s):  
Glycogen Storage Disease ◽  
Plasma Glucose ◽  
Storage Disease ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Glycogen Storage ◽  
Endogenous Glucose Production ◽  
Hepatic Glycogen ◽  
Type I ◽  
Glucose Flux

Children with glycogen storage disease type I (GSD I) lack the ability to convert glucose 6-phosphate to glucose and yet are able to produce glucose endogenously. To test the hypothesis that the source of this glucose is increased cycling of glucose moieties through hepatic glycogen, six children with GSD I were studied on two occasions during which they received enteral glucose for 6 h at 35 or 50 mumol.kg-1.min-1 along with [6,6-2H2]glucose to measure plasma glucose flux and [1-13C]galactose to label intrahepatic uridyl diphosphate (UDP)-glucose. After 3 h, acetaminophen was given to estimate UDP-glucose flux (reflecting the rate of glycogen synthesis). Mean steady-state plasma glucose concentrations (4.8 +/- 0.2 vs. 5.8 +/- 0.1 mM) and total flux (34.8 +/- 1.7 vs. 47.5 +/- 2.0 mumol.kg-1.min-1) were increased (P < 0.05 or better) on the high-infusion day. Endogenous glucose production was detectable only on the low-infusion day (2.0 +/- 0.5 mumol.kg-1.min-1). UDP-glucose flux was increased (P < 0.05) on the high-infusion day (25.8 +/- 1.6 vs. 34.7 +/- 4.1), ruling out cycling of glucose moieties through glycogen with release of glucose by debrancher enzyme as the source of glucose production.

Differential effect of hyperglycemia and hyperinsulinemia on pathways of hepatic glycogen repletion

1991 ◽  
Vol 260 (5) ◽  
pp. E731-E735 ◽  
Author(s):  
G. I. Shulman ◽  
R. A. DeFronzo ◽  
L. Rossetti
Keyword(s):  
Portal Vein ◽  
Plasma Glucose ◽  
Plasma Insulin ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Group Iii ◽  
Group I ◽  
Group Ii ◽  
Glycogen Repletion

To delineate the roles of hyperglycemia and insulin on the direct vs. indirect pathways of liver glycogen synthesis, we performed euglycemic (group I; n = 8), hyperglycemic (group II; n = 9), and euglycemic pharmacological hyperinsulinemic clamp studies (120 min) with an infusion of [1-13C]glucose in chronically catheterized conscious rats after a 24-h fast. Portal vein plasma glucose concentrations and portal vein plasma insulin concentrations, respectively, obtained at the end of the study in groups I-III were as follows: group I 110 +/- 4 mg/dl, 29 +/- 7 ng/ml; group II 219 +/- 7 mg/dl, 24 +/- 7 ng/ml; and group III 112 +/- 9 mg/dl, 174 +/- 25 ng/ml. Mean liver glycogen concentrations at the end of the three studies were 0.68 +/- 0.07, 1.22 +/- 0.08 (P less than 0.001 compared with groups I and III), and 0.60 +/- 0.17 g/100 g wet wt liver in groups I-III respectively, which yielded hepatic glycogen synthetic rates of 0.16 +/- 0.03, 0.41 +/- 0.04 (P less than 0.001 compared with groups I and III), and 0.13 +/- 0.08 mumol glucosyl U.g liver-1.min-1 in groups I-III, respectively. From the enrichments of 13C in the C-1 and C-6 positions of the glucosyl unit in glycogen compared with the enrichment in the C-1 position in portal vein glucose as determined by 13C- and 1H-NMR, the amount of glycogen synthesized by the direct pathway was calculated to be 18 +/- 2, 41 +/- 3 (P less than 0.0001 compared with groups I and III), and 17 +/- 3% in groups I-III, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of lactate on pathways of glycogen formation in the perfused rat liver

1991 ◽  
Vol 280 (2) ◽  
pp. 415-419 ◽  
Author(s):  
Z Zhang ◽  
J Radziuk
Keyword(s):  
Direct Synthesis ◽  
Liver Perfusion ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Group I ◽  
Lactate Uptake ◽  
Group Ii ◽  
Lactate Infusion ◽  
Glycogen Formation

In order to investigate the roles of lactate as substrate and regulator of hepatic glycogen synthesis, two groups of rat livers were perfused with oxygenated blood for 2 h. The initial perfusate glucose and lactate concentrations of Group I and II were 245 +/- 6.8 and 254 +/- 12.9 mg/dl and 49 +/- 2.6 and 54 +/- 2.2 mg/dl respectively. Labelled glucose was added to the perfusate to assess direct glycogen formation. Either additional glucose (Group I) or lactate (Group II) was added (1 mg/min) to a recirculating liver-perfusion system. Initial lactate uptake and glucose formation was identical in the two groups of studies. For Group I, both glucose and lactate uptake by the liver fell to nearly zero, in spite of increasing glucose concentrations. However, with lactate infusion (Group II), its uptake by the liver was maintained at 0.89 +/- 0.14 mg/min after 120 min. In total, 6.2 +/- 0.7 mg (Group I) or 20.2 +/- 3.9 mg (Group II) of glycogen was formed, 4.0 +/- 0.7 mg or 9.2 +/- 2.0 mg by direct synthesis from glucose and 2.2 +/- 0.3 mg or 11.0 +/- 2.1 mg by gluconeogenic formation, in Groups I and II respectively. With the provision of additional lactate, its uptake by the perfused liver tripled, as did glycogen synthesis. Glucose production doubled when lactate was added instead of glucose. Gluconeogenic formation of glycogen increased by 400%. Surprisingly, direct synthesis from glucose also rose by 130%. These data indicate that continued lactate uptake by the liver with gluconeogenic glycogen formation determines the amount of glycogen formed not only by this route, but also by direct synthesis from glucose.

Carbohydrate metabolism during and after exercise in rats: studies with radioglucose

1985 ◽  
Vol 59 (5) ◽  
pp. 1627-1639 ◽  
Author(s):  
B. Sonne ◽  
H. Galbo
Keyword(s):  
Steady State ◽  
Carbohydrate Metabolism ◽  
Isotope Dilution ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Primary Event ◽  
Chemical Measurements ◽  
Rebound Increase ◽  
Methodological Evaluation ◽  
Glycogen Breakdown

Carbohydrate metabolism in exercise, including regulation of glucose production, was studied by isotope-dilution methods, and these were evaluated. Chronically catheterized rats were examined before, during, and after 45 min of running at either low (LIE) or moderate (MIE) intensity. Glucose production (Ra) and disappearance (Rd), as well as muscular glycogen breakdown (Gly), were estimated by primed constant infusions of [3–3H]- and [U-14 C]glucose, and pyruvate oxidation was estimated by sampling of expired 14CO2. During exercise, Ra increased faster than Rd and was, as were steady-state glucose concentration (G) and Gly, directly related to exercise intensity. During recovery Ra and G decreased rapidly, but after MIE, G showed a rebound increase. 14C estimates and chemical measurements sometimes disagreed. Methodological evaluation showed marked incorporation of label in glycogen, lipid, and protein at rest and mobilization of label during exercise. 14CO2 recovery in expired air ranged from only 50% at rest to 77% during MIE. In conclusion, during exercise, mobilization of hepatic glycogen is a primary event and not secondary to increased muscular demand. During and after exercise, plasma glycogen is not precisely controlled at euglycemic levels. Isotope methods may be used to study carbohydrate metabolism in exercising rats, but the results (especially 14C data) should be interpreted with caution.

scholarly journals Catestatin reduces hyperglycemia in insulin-resistant mice by redirecting glucose-6-phosphate from the gluconeogenic to the glycogenic pathway

2020 ◽  
Author(s):  
Gautam Bandyopadhyay ◽  
Kechun Tang ◽  
Nicholas J.G. Webster ◽  
Geert van den Bogaart ◽  
Sushil K. Mahata
Keyword(s):  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glucose Production ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Cultured Hepatocytes ◽  
Glycogen Accumulation ◽  
Insulin Resistant ◽  
Glucose Levels ◽  
Gsk 3Β

AbstractObjectiveDefects in hepatic glycogen synthesis contribute to postprandial hyperglycemia in type 2 diabetic (T2D) patients. Chromogranin A (CgA) peptide Catestatin (CST: hCgA352-372) inhibits dephosphorylation of glucose 6-phosphate (G6P) and improves glucose tolerance in insulin-resistant mice. Here, we seek to determine whether CST also reduces hyperglycemia by increasing hepatic glycogen synthesis.MethodsWe determined liver glycogen, G6P, and UDP glucose (UDPG); plasma insulin, glucagon, norepinephrine (NE), and epinephrine (EPI) levels, and glycogen synthase (GYS) activities in fed and fasted liver of lean and obese wild-type and genetically obese CST knockout (KO) mice after treatments with saline, CST or insulin. We determined glycogen synthesis and glycogenolysis in cultured hepatocytes. We analyzed phosphorylation signals of GYS2 and GSK-3β by immunoblotting.ResultsCST stimulated glycogen accumulation in fed and fasted liver and in cultured hepatocytes. CST reduced plasma NE and EPI levels, suggesting that CST promotes glycogenesis by inhibiting catecholamine-induced glycogenolysis. CST also directly stimulated glycogenesis and inhibited NE and EPI-induced glycogenolysis in hepatocytes. CST elevated the levels of G6P and UDPG and increased GYS activity, thus redirecting G6P to the glycogenic pathway. CST-KO mice had decreased liver glycogen that was restored by treatment with CST, reinforcing the crucial role that CST plays in hepatic glycogenesis.ConclusionsWe conclude that CST directly promotes the glycogenic pathway and reduces plasma glucose levels in insulin-resistant mice by (i) reducing glucose production from G6P, (ii) increasing glycogen synthesis from G6P via formation of UDPG, and (iii) reducing glycogenolysis.

scholarly journals Carbohydrate metabolism of the isolated perfused liver of normal and genetically obese–hyperglycaemic (ob/ob) mice

1971 ◽  
Vol 125 (3) ◽  
pp. 773-780 ◽  
Author(s):  
Jennifer Elliott ◽  
D. A. Hems ◽  
Anne Beloff-Chain
Keyword(s):  
Carbohydrate Metabolism ◽  
Mouse Liver ◽  
Glycogen Synthesis ◽  
Recessive Gene ◽  
Liver Glycogen ◽  
Perfused Liver ◽  
Obese Mice ◽  
Isolated Perfused Liver ◽  
Lactate And Pyruvate ◽  
Glycogen Breakdown

1. A technique for perfusion of the mouse liver has been developed, and aspects of carbohydrate metabolism have been investigated in the perfused liver of normal and genetically obese mice, homozygous for the recessive gene ob. 2. Rates of gluconeogenesis in perfused mouse liver were faster than those reported for slices of mouse liver, particularly from lactate and pyruvate. 3. The rate of glycogen breakdown to glucose, but not to lactate, was faster in liver from fed obese mice. 4. The capacity for glycogen synthesis from glucose was enhanced in liver from 20h-starved obese mice. 5. The capacity for gluconeogenesis from a number of substrates was not significantly altered in livers from fed or starved obese mice when compared with that of lean mice. 6. These results suggest that the liver contributes to the hyperglycaemia of the obese mice by increased glycogenolysis, and that liver glycogen in obese mice is maintained by synthesis from dietary glucose.

scholarly journals Effects of Meal Fructose/Glucose Composition on Postprandial Glucose Appearance and Hepatic Glycogen Synthesis in Healthy Subjects

2021 ◽  
Vol 10 (4) ◽  
pp. 596
Author(s):  
Cristina Barosa ◽  
Rogério T. Ribeiro ◽  
Rita Andrade ◽  
João F. Raposo ◽  
John G. Jones
Keyword(s):  
Plasma Glucose ◽  
Healthy Subjects ◽  
Glycogen Synthesis ◽  
Krebs Cycle ◽  
Hepatic Glycogen ◽  
Indirect Pathway ◽  
Metabolic Complications ◽  
Glucose Ratio ◽  
Dietary Fructose ◽  
P Sources

Dietary fructose overshadows glucose in promoting metabolic complications. Intestinal fructose metabolism (IFM) protects against these effects in rodents, by favoring gluconeogenesis, but the extent of IFM in humans is not known. We therefore aimed to infer the extent of IFM by comparing the contribution of dietary fructose to systemic glucose and hepatic glycogen appearance postprandially. Twelve fasting healthy subjects ingested two protein meals in random order, one supplemented with 50 g 5/95 fructose/glucose (LF) and the other with 50 g 55/45 fructose/glucose (HF). Sources of postprandial plasma glucose appearance and hepatic glycogen synthesis were determined with deuterated water. Plasma glucose excursions, as well as pre- and post-meal insulin, c-peptide, and triglyceride levels were nearly identical for both meals. The total gluconeogenic contribution to plasma glucose appearance was significantly higher for HF versus LF (65 ± 2% vs. 34 ± 3%, p < 0.001). For HF, Krebs cycle anaplerosis accounted for two-thirds of total gluconeogenesis (43 ± 2%) with one-third from Triose-P sources (22 ± 1%). With LF, three-quarters of the total gluconeogenic contribution originated via Krebs cycle anaplerosis (26 ± 2%) with one-quarter from Triose-P sources (9 ± 2%). HF and LF gave similar direct and indirect pathway contributions to hepatic glycogen synthesis. Increasing the fructose/glucose ratio had significant effects on glucose appearance sources but no effects on hepatic glycogen synthesis sources, consistent with extensive IFM. The majority of fructose carbons were converted to glucose via the Krebs cycle.

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