Effects of insulin on liver glycogen synthesis and breakdown in the dog

1965 ◽  
Vol 208 (2) ◽  
pp. 307-316 ◽  
Author(s):  
J. S. Bishop ◽  
R. Steele ◽  
N. Altszuler ◽  
A. Dunn ◽  
C. Bjerknes ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Insulin Infusion ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Percutaneous Biopsy ◽  
Liver Glycogen ◽  
Endogenous Insulin ◽  
Total Glucose ◽  
Almost All

Glucose-C14 was given intravenously in trace amount, as an initial dose followed by continuous infusion, to measure glucose-C12 release by the liver, and total glucose uptake from plasma by the tissues. The glycogen content of liver and the C14 incorporated into the glycogen and the nonglycogen constituents of liver were measured by analysis of percutaneous biopsy samples. Glucose 6-C14 was used to show that direct uptake and conversion to liver glycogen (without passage through three carbon intermediates) of tagged blood glucose molecules was the source of almost all the C14 of glycogen Insulin infusion at 0 1–0.2 U/kg per hr, iv, along with glucose to limit hypoglycemia, stopped glycogen loss, decreased glucose-C12 release, increased glucose uptake from the plasma by the tissues and brought about the incorporation of plasma glucose-C14 units into liver glycogen. Incorporation of C14 into the nonglycogen constituents of the liver was increased much less. Glucose infusion, presumed to stimulate endogenous insulin secretion, produced similar effects. In earlier periods of insulin infusion the outstanding hepatic effects were decreases in glycogen loss and glucose-C12 release. In later periods the outstanding further effect was a great increase in the use of plasma glucose-C14 for liver glycogen synthesis.

Endurance training fails to inhibit skeletal muscle glucose uptake during exercise

1994 ◽  
Vol 76 (5) ◽  
pp. 1876-1881 ◽  
Author(s):  
K. D. Sumida ◽  
C. M. Donovan
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Endurance Training ◽  
Plasma Glucose ◽  
Tibialis Anterior ◽  
Glycogen Content ◽  
Liver Glycogen ◽  
Glycogen Depletion ◽  
Post Exercise ◽  
Skeletal Muscle Glucose Uptake

The effects of endurance training (running 30 m/min, 10% grade for 90 min, 5 days/wk for 12 wk) on skeletal muscle glucose uptake during steady-state exercise (running 20 m/min) were studied in fed rats. A bolus injection of 2-[1,2–3H]deoxyglucose was administered to assess the glucose metabolic index (R′g), an indicator of glucose uptake, in individual tissues of the animal. After 55 min of rest or moderate exercise, various tissues were analyzed for accumulation of phosphorylated 2-[1,2–3H]-deoxyglucose and/or glycogen content. No differences were observed between groups in the resting glycogen content for any of the muscle samples examined. Resting plasma glucose concentrations were not significantly different between groups. Furthermore, no significant differences were observed in R′g between groups for any of the muscle examined (tibialis anterior, extensor digitorum longus, soleus, white gastrocnemius, red gastrocnemius). During exercise, plasma glucose concentrations were not significantly different between groups. Exercise significantly elevated R′g above resting values in the tibialis anterior (5-fold), soleus (3-fold), and red gastrocnemius (7.5-fold). Despite an elevated R′g for specific muscles during exercise, no significant differences were observed in glucose uptake between groups for any tissue examined. Concomitantly, trained animals exhibited significantly less muscle glycogen depletion during exercise compared with control animals. Liver glycogen levels were also significantly higher post-exercise in trained vs. control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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

2008 ◽  
Vol 294 (1) ◽  
pp. E28-E35 ◽  
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.

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.

Metabolic and hormonal changes following endotoxin administration to diabetic rats

1982 ◽  
Vol 243 (1) ◽  
pp. R77-R81
Author(s):  
D. L. Kelleher ◽  
B. C. Fong ◽  
G. J. Bagby ◽  
J. J. Spitzer
Keyword(s):  
Plasma Glucose ◽  
Time Course ◽  
Glycogen Content ◽  
Metabolic Response ◽  
Insulin Response ◽  
Liver Glycogen ◽  
Diabetic Rats ◽  
Hormonal Changes ◽  
Glycogen Depletion ◽  
Endotoxin Administration

The aim of these investigations was to study the time course and cause of the altered metabolic response of diabetic rats to endotoxin administration. Escherichia coli endotoxin was administered to streptozotocin-diabetic and control normoglycemic rats. At 1, 2, 5, 8, and 24 h following endotoxin, animals were decapitated. Plasma samples were analyzed for glucose, lactate, insulin, glucagon, and corticosteroids. In addition, tissue glycogen content of liver and skeletal muscle was determined. Endotoxin caused an elevation of plasma glucose in both diabetic and normoglycemic rats by 1 h postinjection. The elevation was prolonged in diabetic rats for 8 h but lasted only 2 h in nondiabetic rats. Both endotoxin-treated groups demonstrated hyperlactacidemia following endotoxin. Endotoxin led to liver glycogen depletion in both diabetic and normoglycemic rats, whereas muscle glycogen content was only slightly affected. Plasma glucagon and corticosteroids rose immediately and remained elevated in both endotoxin-treated groups. A significant insulin response to rising plasma glucose was observed in nondiabetic but not in diabetic rats following endotoxin. These results suggest that the exaggerated and prolonged hyperglycemia observed in diabetic endotoxin-treated rats is due to hypersecretion of glucose-mobilizing hormones and elevated gluconeogenesis, unmatched by an adequate secretion of insulin to promote glucose uptake and utilization.

Body glucose as fuel for thermogenesis in the white rat exposed to cold

1960 ◽  
Vol 199 (6) ◽  
pp. 1051-1055 ◽  
Author(s):  
Florent Depocas ◽  
Roberto Masironi
Keyword(s):  
Plasma Glucose ◽  
Turnover Rate ◽  
Glycogen Content ◽  
Liver Glycogen ◽  
Turnover Time ◽  
Cold Environments ◽  
Warm Environment ◽  
White Rats ◽  
Liver Glycogen Content ◽  
Carbohydrate Catabolism

Various parameters of glucose metabolism were measured with C14-glucose in unanesthetized warm- and cold-acclimated rats at 30° and 6°C. Exposure of warm-acclimated rats to cold was associated with a decrease in turnover time of plasma glucose, no change in glucose pool size and space, an increase in rates of turnover and oxidation of body glucose, an increase in the ratio of the oxidation rate to the turnover rate, no change in percentage of respiratory CO2 derived from glucose oxidation, and a decrease in liver glycogen content. Approximately reversed changes were observed in cold-acclimated rats transferred from a cold to a warm environment except in the values of turnover time of plasma glucose and terminal liver glycogen content which underwent smaller changes. It is concluded that cold-induced thermogenesis in white rats, whether acclimated to warm or cold environments, is associated with an increase in carbohydrate catabolism proportionate to the increase in energy metabolism.

Plasma free fatty acid turnover during insulin-induced hypoglycemia

1961 ◽  
Vol 201 (3) ◽  
pp. 535-539 ◽  
Author(s):  
D. T. Armstrong ◽  
R. Steele ◽  
N. Altszuler ◽  
A. Dunn ◽  
J. S. Bishop ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Uptake ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Insulin Infusion ◽  
Plasma Free Fatty Acid ◽  
Plasma Glucose Concentration ◽  
Free Insulin ◽  
Adrenal Response

Plasma free fatty acid (FFA) concentration falls when an infusion of glucagon-free insulin is initiated in the normal unanesthetized dog in the postabsorptive state. Using C14 palmitate it was shown that the lowered FFA concentration is caused by decreased FFA production. This decreased FFA production accompanies increased glucose uptake by the tissues as demonstrated using C14 glucose. During slow insulin infusion, when plasma glucose concentration remains above 75 mg%, FFA production and concentration remain low. However, during more rapid insulin infusion, when plasma glucose concentration falls below 50 mg%, the initially lowered FFA production rebounds and FFA production and concentration exceed the preinsulin level. Glucose uptake always remains elevated during insulin infusion. Dibenzyline or guanethidine pretreatment blocks the rebound in FFA production. Thus decreased FFA production, due presumably to decreased FFA release by adipose tissue because of insulin-stimulated glucose uptake, can be overpowered by a sympatho-adrenal response to hypoglycemia during a continued infusion of insulin and a resulting continued increased glucose uptake.

scholarly journals Evaluation of possible mechanisms of three plants for blood glucose control in diabetes

2016 ◽  
Vol 11 (1) ◽  
pp. 224 ◽  
Author(s):  
Damayanthi Dalu ◽  
Satyavati Dhulipala
Keyword(s):  
Glucose Uptake ◽  
Enzyme Inhibition ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Blood Glucose Control ◽  
Inhibition Activity ◽  
Glucose Content ◽  
Cardiac Muscles ◽  
Synthesis Methodology ◽  
Leea Indica

<p class="Abstract">This study was conducted to provide the evidence for the mechanism of  anti-diabetic activity of <em>Cocculus orbiculatus, Leea indica</em> and <em>Ventilago maderaspatana</em>. This was accomplished by employing methods like uptake of glucose, glycogen synthesis and inhibition of α-glucosidase. For uptake of glucose, diaphragms were dissected out in Tyrode solution with 2% glucose and assayed for glucose content. In glycogen synthesis methodology liver, skeletal muscle and cardiac muscles were isolated, homogenized and glycogen content was analyzed. In α-glucosidase enzyme inhibition procedure involved estimation of α-glucosidase enzyme inhibition. All the three plant extracts exhibited significant (p&lt;0.05 - p&lt;0.01) anti-diabetic activity by increasing glucose uptake, glycogen synthesis and inhibiting α-glucosidase enzyme. Among the three plants, <em>V. maderaspatana</em> (500 mg/kg) exhibited higher glucose uptake, glycogen content and α-glucosidase inhibition activity (IC<sub>50</sub> 145 µg/mL). The present experimental results evidenced the anti-diabetic activity of three plants by all the three mechanisms.</p><p> </p>

Shivering thermogenesis and glucose uptake by muscles of normal or diabetic rats

1982 ◽  
Vol 242 (1) ◽  
pp. R109-R115 ◽  
Author(s):  
O. L. Smith ◽  
S. B. Davidson
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Serum Insulin ◽  
Liver Glycogen ◽  
Diabetic Rats ◽  
Glucose Levels ◽  
Severe Diabetes ◽  
Mild Diabetes ◽  
Fasted Rats ◽  
Shivering Thermogenesis

Acute cold exposure of normal rats (4 degrees C for 24 h) increased food intake, reduced plasma glucose and liver glycogen, caused a small increase in plasma free fatty acids, and lowered serum insulin concentration by 50%. In fasted rats, cold raised fatty acid levels twice as high as in fed. In mild diabetes (40 mg/kg streptozotocin iv) cold reduced glucose levels in blood and urine, but in severe diabetes (90 mg/kg) cold aggravated hyperglycemia and ketonuria. Changes in muscle glucose utilization were also studied, after evisceration (functional hepatectomy) of rats from each group. Uptake was calculated from the fall in plasma glucose concentration during the 4-h period after a load of 50% glucose iv. Cold normally increased uptake 67%, but it failed to do so in fasted rats. In diabetic rats, cold enhanced uptake, but only if the disease were mild or insulin controlled. Sensitivity of uptake to insulin was unaffected by cold. The results suggest that shivering thermogenesis, like exercise, can promote glucose uptake by skeletal muscle, if enough insulin is present to prevent excess mobilization of lipid substrates.

scholarly journals Liver Plays a Major Role in FGF-21 Mediated Glucose Homeostasis

2018 ◽  
Vol 45 (4) ◽  
pp. 1423-1433 ◽  
Author(s):  
Mingyao Liu ◽  
Hongwei Cao ◽  
Yuting Hou ◽  
Guopeng Sun ◽  
Deshan Li ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Plasma Glucose ◽  
Glycogen Synthesis ◽  
Glycogen Storage ◽  
Glucose Absorption ◽  
Liver Cells ◽  
Dependent Manner ◽  
Diabetic Mice ◽  
Glut1 Expression

Background/Aims: The liver is a vital organ in vertebrates and has a wide range of functions, including glucose absorption, glycogen storage and glucose production. Fibroblast growth factor (FGF)-21 is a metabolic regulator that is primarily produced by the liver. In this paper, we studied the effect of FGF-21 on glucose metabolism in the liver. Methods: The glucose uptake of cells was detected by 2-Deoxy-d-[3H] glucose; the synergy between insulin and FGF-21 was evaluated. The mRNA expression of GLUT1-4, G6Pase and PEPCK was detected by real-time PCR. Glycogen synthesis was examined by the anthrone method. Blood samples to monitor glucose in db/db diabetic mice were obtained by tail snip. Glucose metabolism in the liver and adipose tissues was observed by fluorescence microscopy. Results: In this study, FGF-21 stimulated glucose uptake by liver cells in both a dose and time-dependent manner, and at the same time, FGF-21 specifically stimulated GLUT1 expression in the liver cells. Furthermore, FGF-21 demonstrated a synergistic effect with insulin on glucose absorption, which is in accordance with enhanced GLUT-1 and -4 expression. Treatment with FGF-21 increased glycogen storage in liver cells. Consistent with in vitro results, FGF-21 lowered the plasma glucose level and stimulated GLUT1 expression and glycogen synthesis in db/db diabetic mice. Simultaneously, FGF-21 inhibited the gene expression of G6Pase and PEPCK. Conclusion: Our results suggest that FGF-21 clears up plasma glucose by stimulating glucose absorption in the liver of diabetic animals and decreases glucose release from the liver by inhibiting gluconeogenesis. Overall, these data indicate that the liver is an important target organ of FGF-21 to regulate glucose metabolism.

scholarly journals Hydrogen Sulfide Impairs Glucose Utilization and Increases Gluconeogenesis in Hepatocytes

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 114-126 ◽  
Author(s):  
Ling Zhang ◽  
Guangdong Yang ◽  
Ashley Untereiner ◽  
Youngjun Ju ◽  
Lingyun Wu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Hepg2 Cells ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Utilization ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Primary Mouse ◽  
Amp Activated Protein Kinase

Mounting evidence has established hydrogen sulfide (H2S) as an important gasotransmitter with multifaceted physiological functions. The aim of the present study was to investigate the role of H2S on glucose utilization, glycogen synthesis, as well as gluconeogenesis in both HepG2 cells and primary mouse hepatocytes. Incubation with NaHS (a H2S donor) impaired glucose uptake and glycogen storage in HepG2 cells via decreasing glucokinase activity. Adenovirus-mediated cystathionine γ-lyase (CSE) overexpression increased endogenous H2S production and lowered glycogen content in HepG2 cells. Glycogen content was significantly higher in liver tissues from CSE knockout (KO) mice compared to that from wild type (WT) mice in fed condition. Glucose consumption was less in primarily cultured hepatocytes isolated from WT mice than those from CSE KO mice, but more glucose was produced by hepatocytes via gluconeogenesis and glycogenolysis pathways in WT mice than in CSE KO mice. NaHS treatment reduced the phosphorylation of AMP-activated protein kinase, whereas stimulation of AMP-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside reversed H2S-impaired glucose uptake. H2S-increased glucose production was likely through increased phosphoenolpyruvate carboxykinase activity. In addition, insulin at the physiological range inhibited CSE expression, and H2S decreased insulin-stimulated phosphorylation of Akt in HepG2 cells. CSE expression was increased, however, in insulin-resistant state induced by exposing cells to high levels of insulin (500 nm) and glucose (33 mm) for 24 h. Taken together, these data suggest that the interaction of H2S and insulin in liver plays a pivotal role in regulating insulin sensitivity and glucose metabolism.

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