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.

Reduced running endurance in gluconeogenesis-inhibited rats

1986 ◽  
Vol 251 (1) ◽  
pp. R137-R142 ◽  
Author(s):  
H. B. John-Alder ◽  
R. M. McAllister ◽  
R. L. Terjung
Keyword(s):  
Fatty Acid ◽  
Blood Glucose ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Plasma Free Fatty Acid ◽  
Hepatic Glycogen ◽  
Endurance Time ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Lactate Levels ◽  
Blood Lactate Levels

The functional significance of gluconeogenesis in prolonging endurance during submaximal activity was assessed in untrained and endurance-trained rats. Gluconeogenesis was inhibited at the phosphoenolpyruvate carboxykinase reaction by 3-mercaptopicolinic acid (3-MPA). Endurance was significantly reduced by 3-MPA in untrained (-32%; P less than 0.005) and in trained rats (-26%; P less than 0.001). Metabolic correlates of fatigue were examined in trained rats. At exhaustion, 3-MPA-treated rats had only 3% of resting hepatic glycogen, 46% of resting white quadriceps glycogen, and 37% of resting blood glucose. All of these substrates were at higher levels in sham-injected controls after the same duration of running (130 min). Glycogen levels in red quadriceps, blood lactate levels, and blood glycerol levels were not different between groups. Plasma free fatty acid levels were elevated to the same extent in both groups after 90 min of activity, remained high at 130 min in controls, but had returned to resting levels in the severely hypoglycemic 3-MPA-treated rats at exhaustion. The results indicate that gluconeogenesis is important for maintaining blood glucose levels and for prolonging endurance time during submaximal activity.

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.

CHANGES IN BLOOD GLUCOSE AND LIVER CARBOHYDRATE AFTER INTRAUTERINE INJECTION OF GLUCAGON INTO FOETAL RATS

1969 ◽  
Vol 45 (3) ◽  
pp. 367-374 ◽  
Author(s):  
D. J. S. HUNTER
Keyword(s):  
Blood Glucose ◽  
Liver Glycogen ◽  
Maternal Blood ◽  
Uterine Wall ◽  
Control Group ◽  
Hepatic Glycogen ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Carbohydrate Levels ◽  
Foetal Blood

SUMMARY Maternal blood glucose, foetal blood glucose and liver carbohydrate levels were estimated after foetuses were injected with glucagon through the uterine wall on days 19½, 20½ and 21½ of gestation in the rat. Glucagon had a hyperglycaemic effect in the foetus on all the days studied but the response was greater and more rapid on day 21½ of gestation. Glucagon was shown to decrease liver glycogen on day 20½ and 21½ but again the response was more rapid and more pronounced on day 21½. The normal levels of foetal liver glycogen were similar to those previously found but the normal foetal blood glucose values are lower than previous results. Decrease in liver glycogen observed in the control group of foetuses on day 21½ of gestation together with a loss in foeto-maternal blood glucose relationship on that day of gestation suggest that on day 21½ the foetal rat develops the ability to mobilize hepatic glycogen and thereby to alter its blood glucose level independently from the mother. The significance of the low blood glucose levels found in the foetus is discussed.

Radioautographic Analysis of the Intralobular and Intracellular Distribution of Newly Formed Hepatic Glycogen After Injection of 3H-Galactose

1982 ◽  
Vol 40 ◽  
pp. 164-165
Author(s):  
J. E. Michaels ◽  
J. T. Hung ◽  
R. R. Cardell
Keyword(s):  
Blood Glucose ◽  
Blood Sugar ◽  
Liver Glycogen ◽  
Intracellular Distribution ◽  
Hepatic Glycogen ◽  
Glucose Levels ◽  
Glucocorticoid Hormone ◽  
Blood Glucose Levels ◽  
Overnight Fasting ◽  
Sugar Levels

In normal animals glycogen levels in the liver are closely related to blood sugar levels. High levels of glucose in the blood stimulate uptake of glucose by liver hepatocytes and synthesis of glycogen whereas low blood glucose levels result in breakdown of glycogen and release of glucose into the blood. After adrenalectomy and overnight fasting, liver glycogen levels in the rat are reduced to about 0.03%. The adrenalectomized rat is easily stimulated to form new glycogen by injection of a glucocorticoid hormone such as dexamethasone (DEX).

scholarly journals Comparative Study of 3 Different Brands of Glimperide

2020 ◽  
Keyword(s):  
Blood Glucose ◽  
Ppar Gamma ◽  
Dissolution Time ◽  
Peroxisome Proliferator ◽  
Disintegration Time ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Weight Variation

Glimepiride is an antidiabetic agent used for lowering blood glucose levels. It induces the activity of peroxisome proliferator-activated receptor-gamma (PPAR gamma). It lowers blood glucose levels by binding to ATP-sensitive potassium channel receptors on the surface of pancreatic cells. The purpose of this study was to perform a comparative analysis of different physicochemical parameters (weight variation, hardness, thickness, friability, disintegration time, and dissolution time) of 3 different commercially available brands of glimepiride in the market. Statistical analysis revealed minor variations in the results. It was found that GETRYL showed the highest % dissolution among all the 3 brands whereas AMARYL took the least time to disintegrate. According to the results of the friability test, Diabold shows the highest stability in the friabilator. However, all 3 brands complied with the official pharmacopoeial limits. The quality of the drug largely influences its therapeutic activity. Hence, owing to the similar physicochemical profile, all the 3 brands can be interchangeably used.

Carbohydrate metabolism of mice exposed to simulated changes in gravity

1964 ◽  
Vol 207 (2) ◽  
pp. 411-414 ◽  
Author(s):  
Jiro Oyama ◽  
William T. Platt
Keyword(s):  
Blood Glucose ◽  
Carbohydrate Metabolism ◽  
Exposure Time ◽  
Liver Glycogen ◽  
Critical Function ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Significant Difference ◽  
Glycogen Deposition ◽  
Adrenal Corticosterone

Unrestrained mice were centrifuged for varying periods ranging from 0.5 to 10 hr at 2.5, 5, and 10 x gravity. Liver glycogen and blood glucose levels increased significantly depending on the g load and exposure time. Adrenalectomy completely abolished the glycogen deposition response. The glycogen response was a critical function of the age of mice; unweaned mice did not respond. Blood corticosterone increased significantly prior to the deposition of glycogen. Centrifuged fed mice deposited three times the amount of glycogen of fasted mice. There was no significant difference in the amount of glycogen deposited in centrifuged mice previously starved for 1, 2, or 3 days. It is concluded that the increased glycogen deposited following centrifugation is effected by an increased elaboration of adrenal corticosterone.

VARIATIONS IN GLUCAGON RESPONSE AMONG JUVENILE DIABETICS

PEDIATRICS ◽  
1963 ◽  
Vol 32 (6) ◽  
pp. 1002-1006
Author(s):  
Donnell D. Etzwiler
Keyword(s):  
Blood Glucose ◽  
Good Control ◽  
Liver Glycogen ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Juvenile Diabetics ◽  
Glycogen Stores ◽  
Initial Blood ◽  
Hyperglycemic Effect

Glucagon or a placebo preparation was administered to 65 juvenile diabetics on 74 separate occasions. When the initial blood glucose of these children showed them to be in reasonably good control, glucagon produced a hyperglycemic effect. However, when the blood glucose levels were markedly elevated, the effect of glucagon was less predictable. The depletion of liver glycogen stores and the possible effect of contaminating insulin in glucagon preparations are discussed.

Endurance training attenuates stress hormone responses to exercise in fasted rats

1982 ◽  
Vol 243 (1) ◽  
pp. R179-R184 ◽  
Author(s):  
W. W. Winder ◽  
M. A. Beattie ◽  
R. T. Holman
Keyword(s):  
Blood Glucose ◽  
Plasma Concentrations ◽  
Liver Glycogen ◽  
Stress Hormone ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Fasted State ◽  
Hormone Responses ◽  
Exercise Muscle ◽  
Fasted Rats

Endurance exercise training produces major adaptations in hormonal and metabolic responses to exercise. This study was designed to determine whether the differences in hormone response persist in the fasted condition when liver glycogen is depleted. Rats were run on a motor-driven rodent treadmill 5 days/wk for periods up to 2 h/day for 10 wk. Trained and nontrained rats were then fasted 24 h and were run for periods ranging from 0- to 60 min. At the end of 60 min of exercise muscle glycogen was higher in trained rats (2.9 +/- 0.3 vs. 1.1 +/- 0.1 mg/g). Blood glucose was maintained at higher levels in trained rats throughout the course of the exercise (3.2 +/- 0.1 vs. 2.3 +/- 0.1 mM after 60 min). Plasma concentrations of glucagon and epinephrine increased in both groups during the exercise but were significantly lower in trained animals. Differences between trained and nontrained animals in stress hormone responses to exercise persist in the fasted state and appear to be a consequence of the capacity of trained animals to maintain higher blood glucose levels.

Liver glycogen content decreases during meals in rats

1982 ◽  
Vol 243 (3) ◽  
pp. R450-R453
Author(s):  
W. Langhans ◽  
N. Geary ◽  
E. Scharrer
Keyword(s):  
Blood Glucose ◽  
Glycogen Content ◽  
Liver Glycogen ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Liver Glycogen Content ◽  
Ad Libitum ◽  
Portal Veins ◽  
Hepatic Portal

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.

scholarly journals Role of PPAR in Hepatic Carbohydrate Metabolism

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Annelies Peeters ◽  
Myriam Baes
Keyword(s):  
Lipid Metabolism ◽  
Blood Glucose ◽  
Carbohydrate Metabolism ◽  
Glucose Homeostasis ◽  
Tight Control ◽  
Master Regulator ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Ppar Ligands

Tight control of storage and synthesis of glucose during nutritional transitions is essential to maintain blood glucose levels, a process in which the liver has a central role. PPAR is the master regulator of lipid metabolism during fasting, but evidence is emerging for a role of PPAR in balancing glucose homeostasis as well. By using PPAR ligands and PPAR mice, several crucial genes were shown to be regulated by PPAR in a direct or indirect way. We here review recent evidence that PPAR contributes to the adaptation of hepatic carbohydrate metabolism during the fed-to-fasted or fasted-to-fed transition in rodents.

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