scholarly journals N6-methyladenosine modification governs liver glycogenesis by stabilizing the glycogen synthase 2 mRNA

2021 ◽  
Author(s):  
Xiang Zhang ◽  
Huilong Yin ◽  
Xiaofang Zhang ◽  
Xunliang Jiang ◽  
Yongkang Liu ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Molecular Mechanism ◽  
Knockout Mice ◽  
Glycogen Synthase ◽  
Critical Role ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Hepatic Glycogen

Abstract Hepatic glycogen is the main source of blood glucose and controls the intervals between meals in mammals. Hepatic glycogen storage in mammalian pups is insufficient compared to their adult counterparts; however, the detailed molecular mechanism is poorly understood. Here, we showed that, similar to glycogen storage pattern, N6-methyladenosine (m6A) modification in mRNAs gradually increases during the growth of mice in liver. Strikingly, in the liver-specific Mettl3 knockout mice, loss of m6A modification disrupts liver glycogen storage. On the mechanism, we screened and identified that glycogen synthase 2 (Gys2) plays a critical role in m6A-mediated regulation of liver glycogen storage. Furthermore, IGF2BP2, as a “reader” of m6A, stabilizes the mRNA of Gys2. More importantly, reconstitution of GYS2 rescues liver glycogenesis in Mettl3-cKO mice. Collectively, a METTL3-IGF2BP2-GYS2 axis, in which METTL3 and IGF2BP2 regulate glycogenesis as “writer” and “reader” respectively, plays a critical role on maintenance of liver glycogenesis in mammals.

scholarly journals CREBH Maintains Circadian Glucose Homeostasis by Regulating Hepatic Glycogenolysis and Gluconeogenesis

2017 ◽  
Vol 37 (14) ◽  
Author(s):  
Hyunbae Kim ◽  
Ze Zheng ◽  
Paul D. Walker ◽  
Gregory Kapatos ◽  
Kezhong Zhang
Keyword(s):  
Blood Glucose ◽  
Glucose Homeostasis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Hepatic Glycogen ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Blood Glucose Levels

ABSTRACT Cyclic AMP-responsive element binding protein, hepatocyte specific (CREBH), is a liver-enriched, endoplasmic reticulum-tethered transcription factor known to regulate the hepatic acute-phase response and lipid homeostasis. In this study, we demonstrate that CREBH functions as a circadian transcriptional regulator that plays major roles in maintaining glucose homeostasis. The proteolytic cleavage and posttranslational acetylation modification of CREBH are regulated by the circadian clock. Functionally, CREBH is required in order to maintain circadian homeostasis of hepatic glycogen storage and blood glucose levels. CREBH regulates the rhythmic expression of the genes encoding the rate-limiting enzymes for glycogenolysis and gluconeogenesis, including liver glycogen phosphorylase (PYGL), phosphoenolpyruvate carboxykinase 1 (PCK1), and the glucose-6-phosphatase catalytic subunit (G6PC). CREBH interacts with peroxisome proliferator-activated receptor α (PPARα) to synergize its transcriptional activities in hepatic gluconeogenesis. The acetylation of CREBH at lysine residue 294 controls CREBH-PPARα interaction and synergy in regulating hepatic glucose metabolism in mice. CREBH deficiency leads to reduced blood glucose levels but increases hepatic glycogen levels during the daytime or upon fasting. In summary, our studies revealed that CREBH functions as a key metabolic regulator that controls glucose homeostasis across the circadian cycle or under metabolic stress.

scholarly journals Effects in vivo of food deprivation and 3-mercaptopicolinate in the glycogen-storage-disease (gsd/gsd) rat

1985 ◽  
Vol 231 (3) ◽  
pp. 755-759 ◽  
Author(s):  
D G Clark ◽  
M Brinkman ◽  
S D Neville ◽  
W D Haynes
Keyword(s):  
Blood Glucose ◽  
Food Deprivation ◽  
Intraperitoneal Injection ◽  
Storage Disease ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Hepatic Glycogen ◽  
Glycogen Stores ◽  
Female Control

Intraperitoneal injection of 3-mercaptopicolinate into 24 h-food-deprived 27-week-old female control (GSD/GSD) rats lowered the concentration of circulating glucose by 66%, but glycerol and lactate concentrations were increased up to 3- and 4-fold respectively. In phosphorylase b kinase-deficient (gsd/gsd) rats the corresponding changes for blood glucose, lactate and glycerol were half those observed in the controls. Although the concentration of liver glycogen (approx. 12%, w/w) in the gsd/gsd rats was not altered during food deprivation, total hepatic glycogen was decreased by 17%. It is suggested that the gradual breakdown of the extensive hepatic glycogen stores during starvation assists in the maintenance of normoglycaemia in the gsd/gsd rat.

Metabolic effects of oral fructose in the liver of fasted rats

1984 ◽  
Vol 247 (4) ◽  
pp. E505-E512 ◽  
Author(s):  
C. B. Niewoehner ◽  
D. P. Gilboe ◽  
G. A. Nuttall ◽  
F. Q. Nuttall
Keyword(s):  
Uric Acid ◽  
Portal Vein ◽  
Hepatic Vein ◽  
Glycogen Synthase ◽  
Control Level ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Metabolic Effects ◽  
Serum Triglycerides ◽  
Fasted Rats

Twenty-four-hour-fasted rats were given fructose (4 g/kg) by gavage. Fructose absorption and the portal vein, aorta, and hepatic vein plasma fructose, glucose, lactate, and insulin concentrations as well as liver fructose and fructose 1-P, glucose, glucose 6-P, UDPglucose, lactate, pyruvate, ATP, ADP, AMP, inorganic phosphate (Pi), cAMP, and Mg2+, and glycogen synthase I and phosphorylase alpha were measured at 10, 20, 30, 40, 60 and 120 min after gavage. Liver and muscle glycogen and serum uric acid and triglycerides also were measured. Fifty-nine percent of the fructose was absorbed in 2 h. There were modest increases in plasma and hepatic fructose, glucose, and lactate and in plasma insulin. Concentrations in the portal vein, aorta, and hepatic vein plasma indicate rapid removal of fructose and lactate by the liver and a modest increase in production of glucose. The source of the increase in plasma lactate is uncertain. Hepatic glucose 6-P increased twofold; UDPglucose rose transiently and then decreased below the control level. Fructose 1-P increased linearly to a concentration of 3.3 mumol/g wet wt by 120 min. There was no change in ATP, ADP, AMP, cAMP, Pi, or Mg2+. Serum triglycerides and uric acid were unchanged. Glycogen synthase was activated by 20 min without a change in phosphorylase alpha. This occurred with a fructose dose that did not significantly increase either the liver glucose or fructose concentrations. Liver glycogen increased linearly after 20 min, and glycogen storage was equal in liver (38.4%) and muscle (36.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency

2017 ◽  
Vol 30 (4) ◽  
Author(s):  
Çiğdem Seher Kasapkara ◽  
Zehra Aycan ◽  
Esma Açoğlu ◽  
Saliha Senel ◽  
Melek Melahat Oguz ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Glucose Monitoring ◽  
Glycogen Metabolism ◽  
Liver Glycogen ◽  
Postprandial Hyperglycemia ◽  
Hepatic Glycogen ◽  
Case Presentation ◽  
Ketotic Hypoglycemia ◽  
Fasting Hypoglycemia ◽  
Lactic Acidemia

AbstractBackground:Glycogen synthase deficiency, also known as glycogenosis (GSD) type 0 is an inborn error of glycogen metabolism caused by mutations in theCase presentation:Herein we report three new cases of liver glycogen synthase deficiency (GSD0). The first patient presented at the 4 years of age with recurrent hypoglycemic seizures. The second patient who is the brother of the first patient presented at 15 months with asymptomatic incidental hypoglycemia. Glucose monitoring in both patients revealed daily fluctuations from fasting hypoglycemia to postprandial hyperglycemia and lactic acidemia. A third patient was consulted for ketotic hypoglycemia and postprandial hyperglycemia at the 5 years of age.Conclusions:Genetic analyses of the siblings revealed homozygosity for mutation c.736C>T on the

EFFECTS OF PROGESTERONE, OESTRADIOL AND/OR CLOMIPHENE ON LIVER GLYCOGEN AND BLOOD GLUCOSE IN INTACT AND ADRENALECTOMISED RATS DURING DELAYED IMPLANTATION

1974 ◽  
Vol 76 (4) ◽  
pp. 678-688
Author(s):  
M. S. Sankaran ◽  
M. R. N. Prasad
Keyword(s):  
Blood Glucose ◽  
Clomiphene Citrate ◽  
Insulin Level ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Prolonged Administration ◽  
Glucose Levels ◽  
Delayed Implantation ◽  
Blood Glucose Levels ◽  
Induced Changes

ABSTRACT Prolonged administration of progesterone alone caused significant changes in liver glycogen. Oestradiol-17β increased the liver glycogen 18 hours after the treatment. A single administration of clomiphene citrate on day 9 post-coitum (pc) inhibited the oestradiol or progesterone induced increase in hepatic glycogen. Bilateral adrenalectomy on day 3 pc abolished the changes in liver glycogen induced by progesterone, oestradiol and/or clomiphene. Administration of progesterone, oestradiol or clomiphene caused a decrease in blood glucose levels in rats during delayed implantation. Although the effects of progesterone and oestradiol on blood glucose levels were abolished by adrenalectomy, clomiphene induced changes persisted in the adrenalectomised rats. It is concluded that progesterone, oestradiol and/or clomiphene induced changes in liver glycogen are mediated through the adrenal glands. Changes in the blood glucose levels are discussed in relation to increased insulin level in the blood and also in relation to the increased glucocorticoid secretion following various treatments.

scholarly journals The Role of Hormones in the Regulation of Glycogen Metabolism in the Clawed Toad Xenopus Laevis (Daudin)

2019 ◽  
pp. 17-24
Author(s):  
Daphna Atar-Zwillenberg ◽  
Michael Atar ◽  
Gianni Morson ◽  
Udo Spornitz
Keyword(s):  
Blood Glucose ◽  
Xenopus Laevis ◽  
Muscle Glycogen ◽  
Hormonal Regulation ◽  
Glycogen Content ◽  
Glycogen Metabolism ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Lipid Levels ◽  
Liver Glycogen Content

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.

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.

The Effects of Dimethylsulfoxide on Experimental Hepatic Ischemia

Swiss Surgery ◽  
2000 ◽  
Vol 6 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Akyürek ◽  
Kafali ◽  
Muhtaroglu
Keyword(s):  
Blood Glucose ◽  
Vena Cava ◽  
Liver Glycogen ◽  
Hepatic Tissue ◽  
Control Group ◽  
Hepatic Glycogen ◽  
Free Oxygen Radical ◽  
Hepatic Ischemia ◽  
Portal Triad ◽  
Ischemic Period

Aims: The aim of the study is to investigate the effects of dimethylsulfoxide (DMSO), a non-enzymatic free oxygen radical detoxifier, on the alterations observed during hepatic ischemia. Methods: Twenty four albino rabbits were entered into the study. DMSO (500mg/kg) was administered through inferior vena cava following dissection of the portal triad and immediately prior to clamping. The alterations on liver glycogen, blood glucose, ALT, AST, LDH, intracellular ATP, GSH-px, SOD, MDA within the erythrocyte and hepatic tissue MDA were investigated. Results: In the control group, following ischemia, a reduction in blood glucose, hepatic glycogen and ATP levels within the cell and an increase in AST and LDH levels, MDA, GSH-px and SOD levels within the erythrocyte and hepatic tissue MDA level were observed (p < 0.01). In the study group, the blood glucose values increased at 30th minute following ischemia. The increase in LDH level was not statistically significant (p < 0.05). The increase in AST level was significantly lower when compared to the control group (p < 0.05). No effect was observed on ALT and ALP levels. DMSO lowered the reduction in hepatic glycogen level (p < 0.05), GSH-px (p <0.01), MDA (p < 0.05) and ATP (p < 0.05) levels within the erythrocyte and hepatic tissue MDA level (p < 0.01) that were increased following ischemia. The increase in blood SOD level was not statistically significant (p >0.05). Conclusion: DMSO can be administered in attempt to prolong the duration of ischemia or to reduce the adverse effects of ischemia on the hepatic tissue during the existing ischemic period.

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