scholarly journals Nrf2-Mediated Regulation of Skeletal Muscle Glycogen Metabolism

2016 ◽  
Vol 36 (11) ◽  
pp. 1655-1672 ◽  
Author(s):  
Akira Uruno ◽  
Yoko Yagishita ◽  
Fumiki Katsuoka ◽  
Yasuo Kitajima ◽  
Aki Nunomiya ◽  
...  

Nrf2 (NF-E2-related factor 2) contributes to the maintenance of glucose homeostasisin vivo. Nrf2 suppresses blood glucose levels by protecting pancreatic β cells from oxidative stress and improving peripheral tissue glucose utilization. To elucidate the molecular mechanisms by which Nrf2 contributes to the maintenance of glucose homeostasis, we generated skeletal muscle (SkM)-specificKeap1knockout (Keap1MuKO) mice that express abundant Nrf2 in their SkM and then examined Nrf2 target gene expression in that tissue. InKeap1MuKOmice, blood glucose levels were significantly downregulated and the levels of the glycogen branching enzyme (Gbe1) and muscle-type PhKα subunit (Phka1) mRNAs, along with those of the glycogen branching enzyme (GBE) and the phosphorylasebkinase α subunit (PhKα) protein, were significantly upregulated in mouse SkM. Consistent with this result, chemical Nrf2 inducers promotedGbe1andPhka1mRNA expression in both mouse SkM and C2C12 myotubes. Chromatin immunoprecipitation analysis demonstrated that Nrf2 binds theGbe1andPhka1upstream promoter regions. InKeap1MuKOmice, muscle glycogen content was strongly reduced and forced GBE expression in C2C12 myotubes promoted glucose uptake. Therefore, our results demonstrate that Nrf2 induction in SkM increases GBE and PhKα expression and reduces muscle glycogen content, resulting in improved glucose tolerance. Our results also indicate that Nrf2 differentially regulates glycogen metabolism in SkM and the liver.

1980 ◽  
Vol 49 (4) ◽  
pp. 722-728 ◽  
Author(s):  
G. A. Gaesser ◽  
G. A. Brooks

Patterns of postexercise glycogen repletion in heart, skeletal muscle, and liver in the absence of exogenously supplied substrates during the first 4 h of recovery were assessed. Female Wistar rats were run to exhaustion using continuous (1.0 mph, 15% grade) and intermittent (alternate 1-min intervals at 0.5 and 1.5 mph, 15% grade) exercise protocols. Rats at exhaustion were characterized by marked depletion of glycogen in heart (55%), skeletal muscle (94%), and liver (97%). Blood glucose levels at exhaustion (1.33 mumol/g) were only 37% of preexercise levels. There were no significant differences between continuous and intermittent exercise groups for any of the tissue glycogen or blood glucose values. Cardiac muscle was the only tissue capable of complete restoration of glycogen levels while relying exclusively upon endogenous substrates. Concentrations of endogenous substrates present at the end of exercise were insufficient to support restoration of blood glucose levels to preexercise values nor support glycogen repletion in skeletal muscle and liver during the initial 4-h food-restricted postexercise period. With subsequent feeding, skeletal muscle demonstrated a glycogen supercompensation effect at 24 h (181.1 and 191.8% of preexercise levels for continuous and intermittent exercise, respectively). Lactate concentration in all tissues at the point exhaustion (1.5--2.5 times resting levels) were only moderately elevated and returned to preexercise levels within 15 min. It was concluded that lactate removal after exercise contributed only minimally to the repletion of muscle glycogen.


1982 ◽  
Vol 243 (3) ◽  
pp. R450-R453
Author(s):  
W. Langhans ◽  
N. Geary ◽  
E. Scharrer

The effects of feeding on liver glycogen content and blood glucose in the hepatic and hepatic portal veins were investigated in rats. Liver glycogen content decreased about 25% during meals both in rats refed after 12 h food deprivation (23 +/- 1 to 17 +/- 1 mg glycogen/g liver) and in ad libitum-fed rats taking fully spontaneous meals (44 +/- 2 to 32 +/- 2 mg/g). Liver glycogen began to increase within 30 min after meals in ad libitum-fed rats. Hepatic vein blood glucose levels at meal onset (118 +/- 4 mg/dl in the food-deprived rats, 127 +/- 4 in ad libitum-fed rats) and at meal end (155 +/- 3 and 166 +/- 5 mg/dl, respectively) were similar in the two groups. Portal vein blood glucose increased during meals in the previously food-deprived rats (83 +/- 4 to 116 +/- 6 mg/dl) but not in the ad libitum-fed rats (127 +/- 5 to 132 +/- 3 mg/dl). Mechanisms that may elicit prandial glycogenolysis and the possible role of this effect in the production of meal ending satiety are discussed.


Author(s):  
Kenia Mendes Rodrigues Castro ◽  
Rodrigo Leal de Paiva Carvalho ◽  
Geraldo Marco Rosa Junior ◽  
Beatriz Antoniassi Tavares ◽  
Luis Henrique Simionato ◽  
...  

1974 ◽  
Vol 52 (1) ◽  
pp. 119-122 ◽  
Author(s):  
A. W. Taylor ◽  
J. Stothart ◽  
M. A. Booth ◽  
R. Thayer ◽  
S. Rao

Sixteen healthy male subjects classified as sedentary (8) or active (8), exercised to exhaustion on a bicycle ergometer at a load requiring 70% of their maximal aerobic capacity. Biopsy samples of the vastus lateralis muscle were taken at rest and at the time of fatigue. A 12 week training program increased skeletal muscle glycogen content and branching enzyme activities twofold. The exhaustive submaximal exercise reduced the glycogen levels of the trained group to values similar to the fatigue levels of the non-trained subjects. Skeletal muscle glycogen branching enzyme activities decreased with submaximal exercise to fatigue in all groups. Maximal exercise to fatigue resulted in small increases in the activities of the enzyme. The results of the present study and a previous study (Taylor et al. 1972. Can. J. Physiol. Pharmacol. 50, 411–415) indicate that the activities of the glycogen synthesizing enzymes are highly correlated with the skeletal muscle resting glycogen concentration and the relative fitness of the subjects.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nasser M Rizk ◽  
Amina Saleh ◽  
Abdelrahman ElGamal ◽  
Dina Elsayegh ◽  
Isin Cakir ◽  
...  

Abstract The Expression of TBC1 Domain Family, member 4 (TBC1D4) in Skeletal Muscles of Insulin-Resistant Mice in Response to Sulforaphane. Background: Obesity is commonly accompanied by impaired glucose homeostasis. Decreased glucose transport to the peripheral tissues, mainly skeletal muscle, leads to reduced total glucose disposal and hyperglycemia. TBC1D4 gene is involved in the trafficking of GLUT4 to the outer cell membrane in skeletal muscle. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound acting by reducing blood glucose levels through mechanisms not fully understood (1). The aim of this study is to investigate the effects SFN on TBC1D4 and GLUT4 gene expression in skeletal muscles of DIO mice, in order to elucidate the mechanism(s) through which SFN improves glucose homeostasis. Methodology: C57BL/6 mice (n=20) were fed with a high fat diet (60%) for 16 weeks to generate diet induced obese (DIO) mice with body weights between 45–50 gm. Thereafter, DIO mice received either SFN (5mg/kg BW) (n=10) or vehicle (n=10) as controls daily by intraperitoneal injections for four weeks. Glucose tolerance test (1g/kg BW, IP) and insulin sensitivity test (ITT) were conducted (1 IU insulin/ g BW, IP route) at the beginning and end of the third week of the injection. At the end of 4 weeks of the injection, samples of blood and skeletal muscles of both hindlimbs were collected. The expression levels of GLUT4 and TBC1D4 genes were analyzed by qRT-PCR. Blood was also used for glucose, adiponectin and insulin measurements. Results: SFN-treated DIO mice had significantly lower non-fasting blood glucose levels than vehicle-treated mice (194.16 ± 14.12 vs. 147.44 ± 20.31 mg/dL, vehicle vs. SFN, p value=0.0003). Furthermore, GTT results indicate that the blood glucose levels at 120 minutes after glucose infusion in was (199.83±34.53 mg/dl vs. 138.55±221.78 mg/dl) for vehicle vs. SFN with p=0.0011 respectively. ITT showed that SFN treatment did not enhance insulin sensitivity in DIO mice. Additionally, SFN treatment did not significantly change the expression of TBC1D4, and GLUT4 genes in skeletal muscles compared to vehicle treatment (p values >0.05). Furthermore, SFN treatment did not significantly affect the systemic insulin (1.84±0.74 vs 1.54±0.55 ng/ml, p=0.436), or adiponectin (11.96 ±2.29 vs 14.4±3.33 ug/ml, p=0.551) levels in SFN vs. vehicle-treated DIO mice, respectively. Conclusion: SFN treatment improves glucose disposal in DIO mice, which is not linked to the gene expression of GLUT4 and TBC1D4 and its mechanism of glucose disposal in skeletal muscles. Furthermore, SFN treatment did not improve insulin level, and the insulin sensitizer hormone adiponectin as potential players for enhancing insulin sensitivity. 1. Axelsson AS, Tubbs E, Mecham B, Chacko S, Nenonen HA, Tang Y, et al. Sci Transl Med. 2017;9(394).


2019 ◽  
pp. 17-24
Author(s):  
Daphna Atar-Zwillenberg ◽  
Michael Atar ◽  
Gianni Morson ◽  
Udo Spornitz

The hormonal regulation of amphibian glycogen metabolism was studied in Xenopus laevis as a typical member of the anurans (tailless amphibians).The main focus of this study was given to the effects of various hormones on the glycogen/glucose balance in adult toads. We determined biochemically the liver and muscle glycogen contents as well as the blood glucose and lipid levels for a number of hormones and also diabetes inducing substances. Additionally, we examined ultrastructure changes in hepatocytes induced by the various treatments, and also investigated the activity of carbohydrate-relevant enzymes by histochemistry. With one exception, the liver glycogen content of Xenopus remained basically unchanged by the treatments or was even slightly enhanced. Only human chorionic gonadotropin, through which the vitellogenic response is triggered, prompts a significant decrease of liver glycogen in females. Under the same conditions the male liver glycogen content remained stable. Muscle glycogen contents were not affected by any of the treatments. Blood glucose and lipid levels on the other hand were elevated considerably in both sexes after application of either epinephrine or cortisol. The ultrastructural examination revealed a proliferation of Rough Endoplasmic Reticulum (RER) in hepatocytes from epinephrine treated toads of both sexes as well as from HCG treated females. By histochemistry, we detected an elevated glucose-6-phosphatase activity in the hepatocytes from toads treated with either epinephrine or cortisol. These treatments also led to enhanced glycogen phosphorylase activity in males, and to a slightly elevated glyceraldehyde-3-phosphate dehydrogenase activity in females. Our results show that the hepatic glycogen is extremely stable in adult Xenopus. Only vitellogenesis causes a marked utilization of glycogen. Since the blood glucose levels are elevated in epinephrine or cortisol treated toads without the liver glycogen being affected, we conclude that either protein and/or lipid metabolism are involved in carbohydrate metabolism in Xenopus laevis.


Author(s):  
Mohammed Ajebli ◽  
Ayoub Amssayef ◽  
Mohamed Eddouks

Aims: The current study was carried out in order to assess the antihyperglycemic effect of Scorzonera undulata (S. undulata). Backgroud: Scorzonera undulata subsp. deliciosa (DC.) Maire is used in the Moroccan pharmacopeia for managing diabetes. Objective: The objective of the study was to evaluate the anithyperglycemic activity in normal and streptozotocin (STZ)- induced diabetic rats as well as the acute toxicity of the aqueous extract of the roots of Scorzonera undulata (S. undulata). Methods: This study investigated the effects of the root aqueous extract of Scorzonera undulata (AERSU) at a dose of 20 mg/kg on blood glucose levels in normal and streptozotocin(STZ)-induced diabetic rats and the acute toxicity of AERSU was examined. Histopathological examination, preliminary phytochemical investigation, determination of glycogen content and evaluation of α-amylase were also performed. Result: Both single and repeated oral doses of AERSU (20 mg/kg) produced a significant reduction of blood glucose levels in normal and diabetic rats. Furthermore, repeated oral administration of AERSU during 15 days increased the glycogen content in the liver in both normal and diabetic rats, inhibited α-amylase activity and improved the histological architecture of the liver and pancreas in treated diabetic rats and ameliorated some biochemical parameters such as ALT and AST. In addition, the preliminary phytochemical investigation showed the richness of the roots of S. undulata in certain phytochemicals particularly in polyphenols. Conclusion: AERSU exhibits an evident antihyperglycemic activity. This pharmacological effect may be due at least to protection of surviving pancreatic β cells, to the protection of hepatocytes, to α-amylase inhibitory effect and to the improvement of glycogen storage in the liver. The dose used in this study seems to be free of any toxicity.


1992 ◽  
Vol 262 (4) ◽  
pp. E434-E439 ◽  
Author(s):  
L. Coderre ◽  
A. K. Srivastava ◽  
J. L. Chiasson

The effect of hypercorticism on the regulation of glycogen metabolism by epinephrine was examined in skeletal muscles using a hindlimb perfusion technique. Rats were injected with either saline or dexamethasone (0.4 mg.kg-1.day-1) for 14 days and were studied in the fed and fasted (24 h) states under saline or epinephrine (10(-7) M) treatment. In the fed state, dexamethasone administration did not affect basal glycogen concentration but decreased glycogen synthase activity ratio in white and red gastrocnemius muscles. Epinephrine failed to decrease glycogen content despite the expected activation of glycogen phosphorylase in the fed dexamethasone-treated rats. Dexamethasone treatment resulted in a threefold increase in the level of muscle adenosine, a phosphorylase a inhibitor. In control rats, fasting was associated with a decrease in muscle glycogen concentration (P less than 0.01) and with an increase in the glycogen synthase activity ratio. Dexamethasone treatment, however, totally abolished both the decreased muscle glycogen content and glycogen synthase activation observed in fasting controls. In the dexamethasone-treated group, fasting restored the glycogenolytic effect of epinephrine. Interestingly, it was associated with decreased muscle adenosine concentrations. These data indicate that, in the fed state, dexamethasone treatment inhibits skeletal muscle glycogenolysis in response to epinephrine despite phosphorylase activation and glycogen synthase inactivation. It is suggested that this abnormality could be due to the inhibition of phosphorylase a by increased muscle adenosine levels.


2020 ◽  
Vol 23 (1) ◽  
Author(s):  
Hye-Won Yang ◽  
Myeongjoo Son ◽  
Junwon Choi ◽  
Seyeon Oh ◽  
You-Jin Jeon ◽  
...  

Abstract Brown alga (Ishige okamurae; IO) dietary supplements have been reported to possess anti-diabetic properties. However, the effects of IO supplements have not been evaluated on glucose metabolism in the pancreas and skeletal muscle. C57BL/6 N male mice (age, 7 weeks) were arranged in five groups: a chow diet with 0.9% saline (NFD/saline group), high-fat diet (HFD) with 0.9% saline (HFD/saline group). high-fat diet with 25 mg/kg IO extract (HFD/25/IOE). high-fat diet with 50 mg/kg IO extract (HFD/50/IOE), and high-fat diet with 75 mg/kg IO extract (HFD/75/IOE). After 4 weeks, the plasma, pancreas, and skeletal muscle samples were collected for biochemical analyses. IOE significantly ameliorated glucose tolerance impairment and fasting and 2 h blood glucose level in HFD mice. IOE also stimulated the protein expressions of the glucose transporters (GLUTs) including GLUT2 and GLUT4 and those of their related transcription factors in the pancreases and skeletal muscles of HFD mice, enhanced glucose metabolism, and regulated blood glucose level. Our results suggest Ishige okamurae extract may reduce blood glucose levels by improving glucose metabolism in the pancreas and skeletal muscle in HFD-induced diabetes.


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