Gluconeogenic pathway in liver and muscle glycogen synthesis after exercise

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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Effects of Acute Exposure to Bleached Kraft Pulpmill Effluent on Carbohydrate Metabolism of Juvenile Coho Salmon (Oncorhynchus kisutch) During Rest and Exercise

Journal of the Fisheries Research Board of Canada ◽

10.1139/f75-098 ◽

1975 ◽

Vol 32 (6) ◽

pp. 753-760 ◽

Cited By ~ 53

Author(s):

D. J. McLeay ◽

D. A. Brown

Keyword(s):

Plasma Glucose ◽

Muscle Glycogen ◽

Coho Salmon ◽

Liver Glycogen ◽

Plasma Lactate ◽

Mean Values ◽

Glucose Levels ◽

Lactate Levels ◽

Sugar Levels ◽

Glycogen Stores

In the static study (no exercise), liver glycogen stores were unchanged during 12-h exposure to 0.8 of the 96-h LC50; longer exposures caused a progressive decrease to levels one fifth those of controls at 72 h. Plasma glucose levels in fish held in 0.8 LC50 effluent for 3–96 h were elevated; at 96 h, glucose had increased threefold. Mean values for plasma lactate were elevated significantly at 3, 6, 24, 72, and 96 h.In the exercise (swimming one body length per second)–rest study, muscle glycogen levels decreased 53–78% during exercise in water or effluent (0.7 LC50) for 4–12 h, and did not recover during 12-h rest in water. Muscle glycogen for fish exercised for 12 h in effluent and then rested for 4 or 12 h in effluent was lower compared to values for fish exercised in effluent and then rested in water. There was no difference in liver glycogen levels offish exercised in effluent or water for 4–12 h. Values of liver glycogen for fish exercised in effluent for 12 h and then rested for 4, 8, or 12 h in effluent decreased 60–70% compared to fish exercised in water for 12 h and then rested in water and by 55–65% from fish exercised in effluent for 12 h and rested in water for 4–12 h. Plasma glucose levels were elevated one- to fourfold during exercise in water or effluent. Fish resting in water for 4, 8, or 12 h following exercise in water had relatively stable glucose levels; whereas for fish exercised and then rested in effluent the glucose levels increased twofold during resting. Plasma lactate levels were elevated five- to sixfold during exercise in water or effluent for 4–12 h, declining to values 1–2 times those of stock fish within 4-h rest. Plasma lactate levels for fish exercised in effluent and then rested in effluent or water were continually higher than those for fish exercised and rested in water.It was concluded that measurement of carbohydrate metabolites, particularly blood sugar levels, in unexercised fish could prove useful as a rapid method for measuring toxicity of pulpmill effluents and other pollutants.

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Hyperglycemia compensates for diet-induced insulin resistance in liver and skeletal muscle of rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.281.5.r1380 ◽

2001 ◽

Vol 281 (5) ◽

pp. R1380-R1389 ◽

Cited By ~ 13

Author(s):

S. Renee Commerford ◽

Michael E. Bizeau ◽

Heather McRae ◽

Ami Jampolis ◽

Jeffrey S. Thresher ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Muscle Glycogen ◽

Control Diet ◽

Glycogen Synthesis ◽

Male Rats ◽

Indirect Pathway ◽

High Fat ◽

Muscle Glycogen Synthesis ◽

High Sucrose

High-fat and high-sucrose diets increase the contribution of gluconeogenesis to glucose appearance (glc Ra) under basal conditions. They also reduce insulin suppression of glc Ra and insulin-stimulated muscle glycogen synthesis under euglycemic, hyperinsulinemic conditions. The purpose of the present study was to determine whether these impairments influence liver and muscle glycogen synthesis under hyperglycemic, hyperinsulinemic conditions. Male rats were fed a high-sucrose, high-fat, or low-fat, starch control diet for either 1 ( n = 5–7/group) or 5 wk ( n = 5–6/group). Studies involved two 90-min periods. During the first, a basal period (BP), [6-3H]glucose was infused. In the second, a hyperglycemic period (HP), [6-3H]glucose, [6-14C]glucose, and unlabeled glucose were infused. Plasma glucose (BP: 111.2 ± 1.5 mg/dl; HP: 172.3 ± 1.5 mg/dl), insulin (BP: 2.5 ± 0.2 ng/ml; HP: 4.9 ± 0.3 ng/ml), and glucagon (BP: 81.8 ± 1.6 ng/l; HP: 74.0 ± 1.3 ng/l) concentrations were not significantly different among diet groups or with respect to time on diet. There were no significant differences among groups in the glucose infusion rate (mg · kg−1 · min−1) necessary to maintain arterial glucose concentrations at ∼170 mg/dl (pooled average: 6.4 ± 0.8 at 1 wk; 6.4 ± 0.7 at 5 wk), percent suppression of glc Ra (44.4 ± 7.8% at 1 wk; 63.2 ± 4.3% at 5 wk), tracer-estimated net liver glycogen synthesis (7.8 ± 1.3 μg · g liver−1 · min−1 at 1 wk; 10.5 ± 2.2 μg · g liver−1 · min−1at 5 wk), indirect pathway glycogen synthesis (3.7 ± 0.9 μg · g liver−1 · min−1 at 1 wk; 3.4 ± 0.9 μg · g liver−1 · min−1 at 5 wk), or tracer-estimated net muscle glycogenesis (1.0 ± 0.3 μg · g muscle−1 · min−1 at 1 wk; 1.6 ± 0.3 μg · g muscle−1 · min−1 at 5 wk). These data suggest that hyperglycemia compensates for diet-induced insulin resistance in both liver and skeletal muscle.

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

Journal of Clinical Medicine ◽

10.3390/jcm10040596 ◽

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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Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00481.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. E28-E35 ◽

Cited By ~ 67

Author(s):

Michale Bouskila ◽

Michael F. Hirshman ◽

Jørgen Jensen ◽

Laurie J. Goodyear ◽

Kei Sakamoto

Keyword(s):

Skeletal Muscle ◽

Glucose Uptake ◽

Muscle Glycogen ◽

Glycogen Content ◽

Glycogen Synthase ◽

Glycogen Synthesis ◽

Wild Type ◽

Muscle Glycogen Synthesis ◽

Mutant Forms

Insulin promotes dephosphorylation and activation of glycogen synthase (GS) by inactivating glycogen synthase kinase (GSK) 3 through phosphorylation. Insulin also promotes glucose uptake and glucose 6-phosphate (G-6- P) production, which allosterically activates GS. The relative importance of these two regulatory mechanisms in the activation of GS in vivo is unknown. The aim of this study was to investigate if dephosphorylation of GS mediated via GSK3 is required for normal glycogen synthesis in skeletal muscle with insulin. We employed GSK3 knockin mice in which wild-type GSK3α and -β genes are replaced with mutant forms (GSK3α/βS21A/S21A/S9A/S9A), which are nonresponsive to insulin. Although insulin failed to promote dephosphorylation and activation of GS in GSK3α/βS21A/S21A/S9A/S9Amice, glycogen content in different muscles from these mice was similar compared with wild-type mice. Basal and epinephrine-stimulated activity of muscle glycogen phosphorylase was comparable between wild-type and GSK3 knockin mice. Incubation of isolated soleus muscle in Krebs buffer containing 5.5 mM glucose in the presence or absence of insulin revealed that the levels of G-6- P, the rate of [14C]glucose incorporation into glycogen, and an increase in total glycogen content were similar between wild-type and GSK3 knockin mice. Injection of glucose containing 2-deoxy-[3H]glucose and [14C]glucose also resulted in similar rates of muscle glucose uptake and glycogen synthesis in vivo between wild-type and GSK3 knockin mice. These results suggest that insulin-mediated inhibition of GSK3 is not a rate-limiting step in muscle glycogen synthesis in mice. This suggests that allosteric regulation of GS by G-6- P may play a key role in insulin-stimulated muscle glycogen synthesis in vivo.

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Response to intravenous injections of amylin and glucagon in fasted, fed, and hypoglycemic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.264.6.e943 ◽

1993 ◽

Vol 264 (6) ◽

pp. E943-E950 ◽

Cited By ~ 7

Author(s):

A. A. Young ◽

G. J. Cooper ◽

P. Carlo ◽

T. J. Rink ◽

M. W. Wang

Keyword(s):

Plasma Glucose ◽

Insulin Infusion ◽

Sodium Lactate ◽

Plasma Lactate ◽

Glucose Response ◽

Intravenous Injections ◽

Glucose Levels ◽

Fasted State ◽

Islet Hormone ◽

Lactate Levels

The actions of intravenous glucagon and amylin, a newly discovered hyperglycemic pancreatic islet hormone, have been compared in 20-h fasted and fed, lightly anesthetized rats, and in rats made hypoglycemic with an insulin infusion. In fasted animals, amylin (75 nmol/kg) was more effective than glucagon (90 nmol/kg) in increasing plasma glucose (glucose increment 4.55 vs. 1.71 mM, P < 0.001). Amylin elicited a marked increase in plasma lactate, as previously reported, whereas glucagon did not alter plasma lactate. In fed animals, glucagon elicited twice as much increase in plasma glucose as did amylin; amylin again elicited a marked lactate increase that was greater (increment 1.45 vs. 0.97 mM, P < 0.05) and more prolonged than in the fasted state, whereas glucagon was without effect on lactate levels. These findings are consistent with glucagon's known action to promote hyperglycemia from hepatic glycogenolysis and amylin's demonstrated action to promote muscle glycogenolysis and increase lactate supply to the liver. Infusions of sodium lactate that produced plasma lactate increments similar to those evoked by 75 nmol/kg amylin evoked patterns of glucose response in fasted and fed rats similar to those evoked by amylin. Thus increased lactate supply to the liver may account for amylin's hyperglycemic effects. Amylin and glucagon could each restore plasma glucose to control levels in fasted animals made hypoglycemic by insulin infusion (plasma glucose reduced to 3.3 mM). A bolus of 75 nmol/kg amylin was more effective than 180 nmol/kg glucagon, restoring basal glucose levels for > 3 h, whereas glucagon restored it for < 1 h.(ABSTRACT TRUNCATED AT 250 WORDS)

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OPTIMIZING POST-EXERCISE MUSCLE GLYCOGEN SYNTHESIS: CARBOHYDRATE AND AMINO ACID/PROTEIN FEEDINGS

Medicine & Science in Sports & Exercise ◽

10.1097/00005768-199905001-00298 ◽

1999 ◽

Vol 31 (Supplement) ◽

pp. S91

Author(s):

L. J.C. van Loon ◽

W. H.M. Saris ◽

A. J.M. Wagenmakers

Keyword(s):

Amino Acid ◽

Muscle Glycogen ◽

Glycogen Synthesis ◽

Post Exercise ◽

Acid Protein ◽

Muscle Glycogen Synthesis ◽

Exercise Muscle ◽

Amino Acid Protein

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Plasma glucose concentration determines direct versus indirect liver glycogen synthesis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.251.5.e584 ◽

1986 ◽

Vol 251 (5) ◽

pp. E584-E590 ◽

Cited By ~ 2

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.

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