scholarly journals Estrogen Regulates Glucose Metabolism in Cattle Neutrophils Through Autophagy

2021 ◽  
Vol 8 ◽  
Author(s):  
Xinbo Wang ◽  
Yuming Zhang ◽  
Yansong Li ◽  
Mingyu Tang ◽  
Qinghua Deng ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Opposite Effect ◽  
Glycogen Synthesis ◽  
Perinatal Period ◽  
Negative Energy ◽  
Pentose Phosphate ◽  
Polymorphonuclear Neutrophils ◽  
Atp Content ◽  
Gsk 3Β ◽  
Immune Potential

Hypoglycemia resulting from a negative energy balance (NEB) in periparturient cattle is the major reason for a reduced glycogen content in polymorphonuclear neutrophils (PMNs). The lack of glycogen induces PMNs dysfunction and is responsible for the high incidence of perinatal diseases. The perinatal period is accompanied by dramatic changes in sex hormones levels of which estrogen (17β-estradiol, E2) has been shown to be closely associated with PMNs function. However, the precise regulatory mechanism of E2 on glucose metabolism in cattle PMNs has not been elucidated. Cattle PMNs were cultured in RPMI 1640 with 2.5 (LG), 5.5 (NG) and 25 (HG) mM glucose and E2 at 20 (EL), 200 (EM) and 450 (EH) pg/mL. We found that E2 maintained PMNs viability in different glucose conditions, and promoted glycogen synthesis by inhibiting PFK1, G6PDH and GSK-3β activity in LG while enhancing PFK1 and G6PDH activity and inhibiting GSK-3β activity in HG. E2 increased the ATP content in LG but decreased it in HG. This indicated that the E2-induced increase/decrease of ATP content may be independent of glycolysis and the pentose phosphate pathway (PPP). Further analysis showed that E2 promoted the activity of hexokinase (HK) and GLUT1, GLUT4 and SGLT1 expression in LG, while inhibiting GLUT1, GLUT4 and SGLT1 expression in HG. Finally, we found that E2 increased LC3, ATG5 and Beclin1 expression, inhibited p62 expression, promoting AMPK-dependent autophagy in LG, but with the opposite effect in HG. Moreover, E2 increased the Bcl-2/Bax ratio and decreased the apoptosis rate of PMNs in LG but had the opposite effect in HG. These results showed that E2 could promote AMPK-dependent autophagy and inhibit apoptosis in response to glucose-deficient environments. This study elucidated the detailed mechanism by which E2 promotes glycogen storage through enhancing glucose uptake and retarding glycolysis and the PPP in LG. Autophagy is essential for providing ATP to maintain the survival and immune potential of PMNs. These results provided significant evidence for further understanding the effects of E2 on PMNs immune potential during the hypoglycemia accompanying perinatal NEB in cattle.

Abnormal activation of glycogen synthesis in fibroblasts from NIDDM subjects. Evidence for an abnormality specific to glucose metabolism

Diabetes ◽  
1993 ◽  
Vol 42 (4) ◽  
pp. 583-589 ◽  
Author(s):  
A. M. Wells ◽  
I. C. Sutcliffe ◽  
A. B. Johnson ◽  
R. Taylor
Keyword(s):  
Glucose Metabolism ◽  
Glycogen Synthesis

scholarly journals Rhythmic glucose metabolism regulates the redox circadian clockwork in human red blood cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ratnasekhar Ch ◽  
Guillaume Rey ◽  
Sandipan Ray ◽  
Pawan K. Jha ◽  
Paul C. Driscoll ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Mammalian Cells ◽  
Metabolic Flux ◽  
Pentose Phosphate ◽  
Human Red Blood Cells ◽  
Integral Process ◽  
Metabolic Oscillations ◽  
Human Rbcs

AbstractCircadian clocks coordinate mammalian behavior and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.

Carbohydrate and Protein Supplements, an Effective Means for Maintaining Exercise-Induced Glucose Metabolism Homeostasis

2021 ◽  
Vol 11 (6) ◽  
pp. 1120-1128
Author(s):  
Dingguo Ruan ◽  
Hong Deng ◽  
Xiaoyang Xu
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Normal Saline ◽  
Glucose Transporter ◽  
Glycogen Synthesis ◽  
Effective Means ◽  
Recovery Period ◽  
Future Application ◽  
Glut 4 ◽  
Exercise Induced

This study aimed to verify the effects of an independently developed carbohydrate and protein (CHO+P) beverage (7.2% oligosaccharide and 1.6% soy-polypeptide) supplement on exerciseinduced glucose metabolism and associated gene expression. Mice received 1 mL/100 g body weight of normal saline (group C; n = 36) or CHO+P (group E; n = 36) at 30 min before an immediately after exercise. Mice without exercise and supplementation served as normal controls (group NC; n = 9). The expression levels related to glucose metabolism were measured at 0, 4, 12, and 24 h after exercise (n = 9 per group). The blood glucose, insulin, and liver glycogen contents in groups C and E were dramatically lower than group NC immediately after exercise. Those in group E were significantly higher than group C, with few differences between the two. Muscle glycogen was restored more quickly when the CHO+P beverage was consumed compared to normal saline. Furthermore, exercise-induced increase in glucose transporter-4 (GLUT-4) mRNA could be depressed by CHO+P supplementation but enhanced in GLUT-4 protein. Interleukin-6 (IL-6) showed a double peak curve in the recovery period, but IL-6 increased again in group E earlier than group C. These findings confirmed that the beverage has significantly improved time in maintaining blood glucose stability, reducing glycogen consumption, accelerating glycogen resynthesis, and repairing injury in rats. This study suggests the future application of this beverage in humans with experimental support and provides a scientific direction for promoting glycogen synthesis and recovery through nutrition.

Abstract 100: Integrated Cardiac Metabolism In End-Stage Human Heart Failure

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Emily Flam ◽  
Cholsoon Jang ◽  
Ken Bedi ◽  
Danielle Murashige ◽  
Yifan Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Human Heart ◽  
Glycogen Synthesis ◽  
Cardiac Metabolism ◽  
Pentose Phosphate ◽  
Metabolic Changes ◽  
Phospholipid Content ◽  
Human Heart Failure ◽  
Nucleotide Synthesis ◽  
End Stage

Heart failure affects millions of people worldwide with mortality near 50% within five years. This disease is characterized by widespread cardiac and systemic metabolic changes, but a comprehensive evaluation of metabolism in failing human hearts is lacking. Here, we provide a comprehensive depiction of cardiac and systemic metabolic changes in 89 explanted failing and non-failing human hearts through integration of plasma and cardiac tissue metabolomics, genome-wide RNAseq, and proteomic data. The data confirm a profound bioenergetic defect in end-stage human heart failure and demonstrate extensive changes in metabolic homeostasis. The data indicate a substantial defect in fatty acid (FA) use in failing hearts, in particular unsaturated FAs. Reduction of FAs and acyl-carnitines in failing tissue in contrast to concomitant elevations in plasma suggest a defect in import of FAs into the cell, rather than a defect in FA oxidation. Intermediates of glycolysis, the pentose phosphate pathway, and glycogen synthesis are all similarly reduced, as is expression of GLUT1, indicating diminished glucose uptake. However, there was no significant change in tissue pyruvate content, suggesting an increase in lactate utilization. The data suggest increased flux of pyruvate into mitochondria, likely promoting pyruvate oxidation but not pyruvate carboxylation. Blunted anabolic pyruvate flux, in turn, likely leads to insufficient TCA cycle intermediates. Ketone levels were increased in both failing tissue and plasma, as previously reported. The phospholipid content of failing human hearts is greatly increased in both failing tissue and plasma. Nucleotide synthesis pathways also appear to be reprogrammed, with a notable decrease in adenosine metabolism, specifically. Together, these data indicate widespread change in the local cardiac and greater systemic metabolic landscape in severe human heart failure.

Insulin-Sensitive Phospholipid Signaling Systems and Glucose Transport. Update II

2001 ◽  
Vol 226 (4) ◽  
pp. 283-295 ◽  
Author(s):  
Robert V. Farese
Keyword(s):  
Protein Kinase ◽  
Glucose Metabolism ◽  
Glucose Transport ◽  
Intracellular Signaling ◽  
Glucose Transporter ◽  
De Novo ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Cell Types ◽  
Biologically Active

Insulin provokes rapid changes in phospholipid metabolism and thereby generates biologically active lipids that serve as intracellular signaling factors that regulate glucose transport and glycogen synthesis. These changes include: (i) activation of phosphatidylinositol 3-kinase (PI3K) and production of PIP3; (ii) PIP3-dependent activation of atypical protein kinase Cs (PKCs); (iii) PIP3-dependent activation of PKB; (iv) PI3K-dependent activation of phospholipase D and hydrolysis of phosphatidyicholine with subsequent increases in phosphatidic acid (PA) and diacyiglycerol (DAG); (v) PI3K-independent activation of glycerol-3-phosphate acylytansferase and increases in de novo synthesis of PA and DAG; and (vi) activation of DAG-sensitive PKCs. Recent findings suggest that atypical PKCs and PKB serve as important positive regulators of insulin-stimulated glucose metabolism, whereas mechanisms that result in the activation of DAG-sensitive PKCs serve mainly as negative regulators of insulin signaling through PI3K. Atypical PKCs and PKB are rapidly activated by insulin in adipocytes, liver, skeletal muscles, and other cell types by a mechanism requiring PI3K and its downstream effector, 3-phosphoinositide-dependent protein kinase-1 (PDK-1), which, in conjunction with PIP3, phosphorylates critical threonine residues in the activation loops of atypical PKCs and PKB. PIP3 also promotes increases in autophosphorylation and allosteric activation of atypical PKCs. Atypical PKCs and perhaps PKB appear to be required for insulin-induced translocation of the GLUT 4 glucose transporter to the plasma membrane and subsequent glucose transport. PKB also appears to be the major regulator of glycogen synthase. Together, atypical PKCs and PKB serve as a potent, integrated PI3K/PDK-1-directed signaling system that is used by insulin to regulate glucose metabolism.

scholarly journals ROS/PI3K/Akt and Wnt/β-catenin signalings activate HIF-1α-induced metabolic reprogramming to impart 5-fluorouracil resistance in colorectal cancer

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Shuohui Dong ◽  
Shuo Liang ◽  
Zhiqiang Cheng ◽  
Xiang Zhang ◽  
Li Luo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Glucose Metabolism ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Cell Models ◽  
Primary Tumors ◽  
Pharmacological Inhibition ◽  
Potential Biomarker

Abstract Background Acquired resistance of 5-fluorouracil (5-FU) remains a clinical challenge in colorectal cancer (CRC), and efforts to develop targeted agents to reduce resistance have not yielded success. Metabolic reprogramming is a key cancer hallmark and confers several tumor phenotypes including chemoresistance. Glucose metabolic reprogramming events of 5-FU resistance in CRC has not been evaluated, and whether abnormal glucose metabolism could impart 5-FU resistance in CRC is also poorly defined. Methods Three separate acquired 5-FU resistance CRC cell line models were generated, and glucose metabolism was assessed by measuring glucose and lactate utilization, RNA and protein expressions of glucose metabolism-related enzymes and changes of intermediate metabolites of glucose metabolite pool. The protein levels of hypoxia inducible factor 1α (HIF-1α) in primary tumors and circulating tumor cells of CRC patients were detected by immunohistochemistry and immunofluorescence. Stable HIF1A knockdown in cell models was established with a lentiviral system. The influence of both HIF1A gene knockdown and pharmacological inhibition on 5-FU resistance in CRC was evaluated in cell models in vivo and in vitro. Results The abnormality of glucose metabolism in 5-FU-resistant CRC were described in detail. The enhanced glycolysis and pentose phosphate pathway in CRC were associated with increased HIF-1α expression. HIF-1α-induced glucose metabolic reprogramming imparted 5-FU resistance in CRC. HIF-1α showed enhanced expression in 5-FU-resistant CRC cell lines and clinical specimens, and increased HIF-1α levels were associated with failure of fluorouracil analog-based chemotherapy in CRC patients and poor survival. Upregulation of HIF-1α in 5-FU-resistant CRC occurred through non-oxygen-dependent mechanisms of reactive oxygen species-mediated activation of PI3K/Akt signaling and aberrant activation of β-catenin in the nucleus. Both HIF-1α gene knock-down and pharmacological inhibition restored the sensitivity of CRC to 5-FU. Conclusions HIF-1α is a potential biomarker for 5-FU-resistant CRC, and targeting HIF-1a in combination with 5-FU may represent an effective therapeutic strategy in 5-FU-resistant CRC.

scholarly journals Changes in selected biochemical parameters during subclinical and clinical ketosis in dairy cows

2019 ◽  
Vol 74 (10) ◽  
pp. 6133-2019
Author(s):  
YUANYUAN CHEN ◽  
ZHIHAO DONG ◽  
RUIRUI LI ◽  
CHUANG XU
Keyword(s):  
Lipid Metabolism ◽  
Energy Balance ◽  
Dairy Cows ◽  
Perinatal Period ◽  
Oxidative Capacity ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Fibroblast Growth Factor 21 ◽  
Acid Oxidation ◽  
Subclinical Ketosis

Negative energy balance (NEB) is a common pathological cause of ketosis. As the major organs of lipid metabolism, the liver and fat tissue take part in regulating lipid oxidative capacity and energy demands, which is also a key metabolic pathway that regulates NEB development during the perinatal period. Fibroblast Growth Factor 21 (FGF21) is a novel metabolic regulator involved in the control of fatty acid oxidation and lipid metabolism during a prolonged negative energy balance. Our study determined a correlation between serum FGF21 and β-hydroxybutyric acid (BHBA) levels in dairy cows with ketosis. We used sixty cows with low milk yield, abnormal glucose metabolism, and ketosis. Serum FGF21 and BHBA levels were measured using commercial kits. Serum FGF21 increased with increasing BHBA levels up to 1.6 mmol/L. At BHBA levels > 1.6 mmol/L, FGF21 decreased. Serum FGF21 levels were positively associated with BHBA levels, particularly in dairy cows with subclinical ketosis (r = 0.647, P < 0.01). At BHBA levels between 1.2 mmol/L and 1.6 mmol/L, FGF21 was more closely correlated with BHBA than with other metabolic parameters. At BHBA levels > 1.6 mmol/L, the association between FGF21 and BHBA was not significant. In conclusion, our results show that FGF21 was closely related with SK in cows. FGF21 may be a promising regulator in the prevention of subclinical ketosis.

scholarly journals Insulin stimulates glucose metabolism via the pentose phosphate pathway in Drosophila Kc cells

FEBS Letters ◽  
2003 ◽  
Vol 555 (2) ◽  
pp. 307-310 ◽  
Author(s):  
Rolando B. Ceddia ◽  
George J. Bikopoulos ◽  
Arthur J. Hilliker ◽  
Gary Sweeney
Keyword(s):  
Glucose Metabolism ◽  
Pentose Phosphate Pathway ◽  
Pentose Phosphate

Glucose metabolism in epitrochlearis muscle of acutely exercised and trained rats

1986 ◽  
Vol 250 (2) ◽  
pp. E137-E143 ◽  
Author(s):  
T. A. Davis ◽  
S. Klahr ◽  
E. D. Tegtmeyer ◽  
D. F. Osborne ◽  
T. L. Howard ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Acute Exercise ◽  
Glycogen Synthesis ◽  
Prior Training ◽  
Glycogen Stores

Effects of insulin on glycogen synthesis (GS), glycolytic utilization (GU), and glucose uptake (GT) were studied in isolated epitrochlearis muscles from exercise-trained or sedentary rats during recovery from acute exercise or at rest. During the 1st h after acute exercise, the enhanced basal and insulin-stimulated GT was directed mainly toward replenishment of glycogen but basal GU was also increased. During the second through third hours after exercise, basal GS decreased but remained greater than rest and basal GU and GT returned to normal. Insulin sensitivity of these parameters was enhanced. Training alone reduced basal GS but enhanced insulin sensitivity of GT and GU. Training reduced the acute exercise-stimulated increase in basal and insulin sensitivity of GS during recovery from acute exercise, probably due to elevated glycogen stores. Thus recovery from acute exercise or training, either alone or in combination, enhances insulin stimulated GT in muscle; however, the increased glucose is primarily channeled toward GS after acute exercise, which is reduced by prior training and is directed to GU in trained animals either at rest or after acute exercise.

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