Circadian rhythm in sensitivity of glucose metabolism to insulin in rat soleus muscle

1988 ◽  
Vol 255 (1) ◽  
pp. E41-E45 ◽  
Author(s):  
B. Leighton ◽  
J. M. Kowalchuk ◽  
R. A. Challiss ◽  
E. A. Newsholme
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Muscle Glycogen ◽  
Blood Glucose Concentration ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Feeding Period ◽  
Rat Soleus Muscle ◽  
Animal House

This study determined whether the sensitivity of glucose metabolism to insulin in skeletal muscle varies during a 24-h period. Soleus muscles were isolated from ad libitum-fed rats killed at 0900, 1600, 2100, and 0300. The animal house was illuminated between 0800 and 2000. The sensitivities of glycolysis (which is an excellent index of glucose transport) and glycogen synthesis to insulin were greatest in muscles isolated at 0900 and 2100. Marked decreases in sensitivities of both processes to insulin were observed in muscles isolated at 0300 and 1600, which are times halfway through the feeding and postabsorptive periods, respectively. Hence, this study demonstrates circadian changes in the sensitivity of glucose utilization by skeletal muscle to insulin, which may be important in control of blood glucose concentration. Glycogen levels in skeletal muscles were highest at 0300 and lowest at 2100; hepatic glycogen content reached a peak at 0900, and the lowest content was measured at 2100. The liver glycogen level was increased by only 15% midway into the feeding period (i.e., 0300). This suggests that muscle glycogen may act as a temporary store of glucose residues during the feeding period; it stores glycogen in the first half of the feeding period but during the second half some muscle glycogen is converted to lactate, which acts as a precursor for hepatic gluconeogenesis.

Lack of defect in insulin action on hepatic glycogen synthase and phosphorylase in insulin-resistant monkeys

1998 ◽  
Vol 274 (6) ◽  
pp. G1005-G1010
Author(s):  
Heidi K. Ortmeyer ◽  
Noni L. Bodkin
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Rhesus Monkeys ◽  
Insulin Action ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Insulin Resistant

It is well known that an alteration in insulin activation of skeletal muscle glycogen synthase is associated with insulin resistance. To determine whether this defect in insulin action is specific to skeletal muscle, or also present in liver, simultaneous biopsies of these tissues were obtained before and during a euglycemic hyperinsulinemic clamp in spontaneously obese insulin-resistant male rhesus monkeys. The activities of glycogen synthase and glycogen phosphorylase and the concentrations of glucose 6-phosphate and glycogen were measured. There were no differences between basal and insulin-stimulated glycogen synthase and glycogen phosphorylase activities or in glucose 6-phosphate and glycogen contents in muscle. Insulin increased the activities of liver glycogen synthase ( P < 0.05) and decreased the activities of liver glycogen phosphorylase ( P ≤ 0.001). Insulin also caused a reduction in liver glucose 6-phosphate ( P = 0.05). We conclude that insulin-resistant monkeys do not have a defect in insulin action on liver glycogen synthase, although a defect in insulin action on muscle glycogen synthase is present. Therefore, tissue-specific alterations in insulin action on glycogen synthase are present in the development of insulin resistance in rhesus monkeys.

More marked stimulation by lithium than insulin of the glycogenic pathway in rat skeletal muscle.

1997 ◽  
Vol 273 (3) ◽  
pp. E514 ◽  
Author(s):  
C Fürnsinn ◽  
C Noe ◽  
R Herdlicka ◽  
M Roden ◽  
P Nowotny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Zucker Rats ◽  
Kinase Activation ◽  
Insulin Resistant ◽  
Primary Deficit ◽  
Rat Soleus Muscle ◽  
Glycogen Synthase Activity

Lithium's impact on glucose metabolism was compared with that of insulin in isolated rat soleus muscle. Lithium chloride (20 mmol/l) induced a 4.8-fold more pronounced increment over basal glycogen synthase activity than insulin (10 nmol/l) (nmol UDP-glucose into glycogen in synthase activity assay.g-1.min-1: lithium, +22.1 +/- 1.8 vs. insulin, +4.6 +/- 3.9; P < 0.01). In parallel, lithium was less efficient than insulin in stimulating glucose transport (counts per minute 2-deoxy-D-[3H]glucose.mg-1.h-1: lithium, +211 +/- 19 vs. insulin, +311 +/- 57; P < 0.05) and lactate release (mumol.g-1.h-1: lithium, +1.0 +/- 0.5 vs. insulin, +3.9 +/- 0.5; P < 0.01), and similar increments were induced in glycogen synthesis (mumol glucose into glycogen.g-1.h-1: lithium, +3.32 +/- 0.43 vs. insulin, +3.46 +/- 0.47; not significant). Full additivity of glycogenic effects and divergent dependency on phosphatidylinositol 3-kinase activation provided further evidence for different mechanisms of action. In muscle from insulin-resistant obese Zucker rats (fa/fa), failure of lithium to reverse deficits in glucose metabolism suggested a primary deficit in muscle glucose uptake rather than glycogen synthesis. Hence lithium distinctly stimulates glycogen synthase activity in skeletal muscle and may therefore be regarded as a candidate for the treatment of disorders associated with primary deficits in the glycogenic pathway.

scholarly journals Lack of skeletal muscle IL-6 influences hepatic glucose metabolism in mice during prolonged exercise

2017 ◽  
Vol 312 (4) ◽  
pp. R626-R636 ◽  
Author(s):  
Lærke Bertholdt ◽  
Anders Gudiksen ◽  
Camilla L. Schwartz ◽  
Jakob G. Knudsen ◽  
Henriette Pilegaard
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Prolonged Exercise ◽  
Hepatic Glycogen ◽  
Glucose Content ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Single Bout ◽  
Substrate Choice

The liver is essential in maintaining and regulating glucose homeostasis during prolonged exercise. IL-6 has been shown to be secreted from skeletal muscle during exercise and has been suggested to signal to the liver. Therefore, the aim of this study was to investigate the role of skeletal muscle IL-6 on hepatic glucose regulation and substrate choice during prolonged exercise. Skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice (age, 12–14 wk) and littermate lox/lox (Control) mice were either rested (Rest) or completed a single bout of exercise for 10, 60, or 120 min, and the liver was quickly obtained. Hepatic IL-6 mRNA was higher at 60 min of exercise, and hepatic signal transducer and activator of transcription 3 was higher at 120 min of exercise than at rest in both genotypes. Hepatic glycogen was higher in IL-6 MKO mice than control mice at rest, but decreased similarly during exercise in the two genotypes, and hepatic glucose content was lower in IL-6 MKO than control mice at 120 min of exercise. Hepatic phosphoenolpyruvate carboxykinase mRNA and protein increased in both genotypes at 120 min of exercise, whereas hepatic glucose 6 phosphatase protein remained unchanged. Furthermore, IL-6 MKO mice had higher hepatic pyruvate dehydrogenase (PDH)Ser232 and PDHSer300 phosphorylation than control mice at rest. In conclusion, hepatic gluconeogenic capacity in mice is increased during prolonged exercise independent of muscle IL-6. Furthermore, Skeletal muscle IL-6 influences hepatic substrate regulation at rest and hepatic glucose metabolism during prolonged exercise, seemingly independent of IL-6 signaling in the liver.

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.

Carbohydrate loading failed to improve 100-km cycling performance in a placebo-controlled trial

2000 ◽  
Vol 88 (4) ◽  
pp. 1284-1290 ◽  
Author(s):  
Louise M. Burke ◽  
John A. Hawley ◽  
Elske J. Schabort ◽  
Alan St Clair Gibson ◽  
Iñigo Mujika ◽  
...  
Keyword(s):  
Body Mass ◽  
Muscle Glycogen ◽  
Blood Glucose Concentration ◽  
Controlled Trial ◽  
Liver Glycogen ◽  
Cycling Performance ◽  
Controlled Study ◽  
Mean Power ◽  
Road Racing ◽  
Mean Power Output

We evaluated the effect of carbohydrate (CHO) loading on cycling performance that was designed to be similar to the demands of competitive road racing. Seven well-trained cyclists performed two 100-km time trials (TTs) on separate occasions, 3 days after either a CHO-loading (9 g CHO ⋅ kg body mass− 1 ⋅ day− 1) or placebo-controlled moderate-CHO diet (6 g CHO ⋅ kg body mass− 1 ⋅ day− 1). A CHO breakfast (2 g CHO/kg body mass) was consumed 2 h before each TT, and a CHO drink (1 g CHO ⋅ kg.body mass− 1 ⋅ h− 1) was consumed during the TTs to optimize CHO availability. The 100-km TT was interspersed with four 4-km and five 1-km sprints. CHO loading significantly increased muscle glycogen concentrations (572 ± 107 vs. 485 ± 128 mmol/kg dry wt for CHO loading and placebo, respectively; P < 0.05). Total muscle glycogen utilization did not differ between trials, nor did time to complete the TTs (147.5 ± 10.0 and 149.1 ± 11.0 min; P = 0.4) or the mean power output during the TTs (259 ± 40 and 253 ± 40 W, P = 0.4). This placebo-controlled study shows that CHO loading did not improve performance of a 100-km cycling TT during which CHO was consumed. By preventing any fall in blood glucose concentration, CHO ingestion during exercise may offset any detrimental effects on performance of lower preexercise muscle and liver glycogen concentrations. Alternatively, part of the reported benefit of CHO loading on subsequent athletic performance could have resulted from a placebo effect.

Persistent increase in glucose uptake by rat skeletal muscle following exercise

1981 ◽  
Vol 241 (5) ◽  
pp. C200-C203 ◽  
Author(s):  
J. L. Ivy ◽  
J. O. Holloszy
Keyword(s):  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Muscle Glycogen ◽  
Glycogen Synthesis ◽  
Exercise Stress ◽  
Rat Skeletal Muscle ◽  
Major Pathway ◽  
Glycogen Accumulation ◽  
Hindlimb Muscles ◽  
Muscle Glycogen Concentration

The effect of a bout of exercise on glucose uptake and glycogen synthesis in skeletal muscle was examined using a perfused rat hindlimb preparation. Rats were subjected to a bout of swimming. The exercise stress was moderate as reflected in a reduction of muscle glycogen concentration of only 50%. Glucose uptake and glycogen synthesis were measured in perfused hindlimb muscles for a 30-min period beginning approximately 60 min following the exercise. The rate of glucose uptake in the absence of insulin was 10-fold higher in hindlimbs of exercised animals than in the controls. The rate of glucose uptake was also higher in exercised than in control muscles in the presence of 50 microunits/ml or 10 mU/ml of insulin, but these differences were smaller than that found in the absence of insulin. Conversion to glycogen was the major pathway for disposal of the glucose taken up by muscle. The rate of glycogen accumulation in the exercised plantaris muscles was greater than in the control muscles both in the absence and presence of insulin.

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.

Effects of maternal exercise on liver and skeletal muscle glycogen storage in pregnant rats

1991 ◽  
Vol 71 (3) ◽  
pp. 1015-1019 ◽  
Author(s):  
M. F. Mottola ◽  
P. D. Christopher
Keyword(s):  
Skeletal Muscle ◽  
Muscle Glycogen ◽  
Glycogen Content ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Treadmill Running ◽  
Control Group ◽  
Skeletal Muscle Glycogen ◽  
Maternal Exercise ◽  
White Gastrocnemius

To examine the effects of maternal exercise on liver and skeletal muscle glycogen storage, female Sprague-Dawley rats were randomly divided into control, nonpregnant runner, pregnant nonrunning control, pregnant runner, and prepregnant exercised control groups. The exercise consisted of treadmill running at 30 m/min on a 10 degree incline for 60 min, 5 days/wk. Pregnancy alone, on day 20 of gestation, decreased maternal liver glycogen content and increased red and white gastrocnemius muscle glycogen storage above control values (P less than 0.05). In contrast, exercise in nonpregnant animals augmented liver glycogen storage and also increased red and white gastrocnemius glycogen content (P less than 0.05). By combining exercise and pregnancy, the decrease in liver glycogen storage in the pregnant nonexercised condition was prevented in the pregnant runner group and more glycogen was stored in both the red and white portions of the gastrocnemius than all other groups (P less than 0.05). Fetal body weight was greatest (P less than 0.05) in the pregnant runner group and lowest (P less than 0.05) in the prepregnant exercise control group. These results demonstrate that chronic maternal exercise may change maternal glycogen storage patterns in the liver and skeletal muscle with some alteration in fetal outcome.

Prolonged suppression of glucose metabolism causes insulin resistance in rat skeletal muscle

1997 ◽  
Vol 272 (2) ◽  
pp. E288-E296 ◽  
Author(s):  
J. K. Kim ◽  
J. H. Youn
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Skeletal Muscles ◽  
Glycogen Synthesis ◽  
Whole Body ◽  
Metabolic Fluxes ◽  
Phosphate Inhibition ◽  
Intracellular Glucose

To determine whether an impairment of intracellular glucose metabolism causes insulin resistance, we examined the effects of suppression of glycolysis or glycogen synthesis on whole body and skeletal muscle insulin-stimulated glucose uptake during 450-min hyperinsulinemic euglycemic clamps in conscious rats. After the initial 150 min to attain steady-state insulin action, animals received an additional infusion of saline, Intralipid and heparin (to suppress glycolysis), or amylin (to suppress glycogen synthesis) for up to 300 min. Insulin-stimulated whole body glucose fluxes were constant with saline infusion (n = 7). In contrast, Intralipid infusion (n = 7) suppressed glycolysis by approximately 32%, and amylin infusion (n = 7) suppressed glycogen synthesis by approximately 45% within 30 min after the start of the infusions (P < 0.05). The suppression of metabolic fluxes increased muscle glucose 6-phosphate levels (P < 0.05), but this did not immediately affect insulin-stimulated glucose uptake due to compensatory increases in other metabolic fluxes. Insulin-stimulated whole body glucose uptake started to decrease at approximately 60 min and was significantly decreased by approximately 30% at the end of clamps (P < 0.05). Similar patterns of changes in insulin-stimulated glucose fluxes were observed in individual skeletal muscles. Thus the suppression of intracellular glucose metabolism caused decreases in insulin-stimulated glucose uptake through a cellular adaptive mechanism in response to a prolonged elevation of glucose 6-phosphate rather than the classic mechanism involving glucose 6-phosphate inhibition of hexokinase.

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