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

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.

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 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.

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.

Hepatic glucose metabolism during intraduodenal glucose infusion: impact of infection

2000 ◽  
Vol 279 (1) ◽  
pp. E108-E115
Author(s):  
Owen P. McGuinness ◽  
Joseph Ejiofor ◽  
D. Brooks Lacy ◽  
Nancy Schrom
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Fibrin Clot ◽  
Glucose Absorption ◽  
Glucose Infusion ◽  
Hepatic Glucose Metabolism ◽  
Hepatic Glucose ◽  
Glycogen Deposition ◽  
Hepatic Glucose Uptake

We previously reported that infection decreases hepatic glucose uptake when glucose is given as a constant peripheral glucose infusion (8 mg · kg−1· min−1). This impairment persisted despite greater hyperinsulinemia in the infected group. In a normal setting, hepatic glucose uptake can be further enhanced if glucose is given gastrointestinally. Thus the aim of this study was to determine whether hepatic glucose uptake is impaired during an infection when glucose is given gastrointestinally. Thirty-six hours before study, a sham (SH, n = 7) or Escherichia coli-containing (2 × 109organisms/kg; INF; n = 7) fibrin clot was placed in the peritoneal cavity of chronically catheterized dogs. After the 36 h, a glucose bolus (150 mg/kg) followed by a continuous infusion (8 mg · kg−1· min−1) of glucose was given intraduodenally to conscious dogs for 240 min. Tracer ([3-3H]glucose and [U-14C]glucose) and arterial-venous difference techniques were used to assess hepatic and intestinal glucose metabolism. Infection increased hepatic blood flow (35 ± 5 vs. 47 ± 3 ml · kg−1· min−1; SH vs. INF) and basal glucose rate of appearance (2.1 ± 0.2 vs. 3.3 ± 0.1 mg · kg−1· min−1). Arterial insulin concentrations increased similarly in SH and INF during the last hour of glucose infusion (38 ± 8 vs. 46 ± 20 μU/ml), and arterial glucagon concentrations fell (62 ± 14 to 30 ± 3 vs. 624 ± 191 to 208 ± 97 pg/ml). Net intestinal glucose absorption was decreased in INF, attenuating the increase in blood glucose caused by the glucose load. Despite this, net hepatic glucose uptake (1.6 ± 0.8 vs. 2.4 ± 0.9 mg · kg−1· min−1; SH vs. INF) and consequently tracer-determined glycogen synthesis (1.3 ± 0.3 vs. 1.0 ± 0.3 mg · kg−1· min−1) were similar between groups. In summary, infection impairs net glucose absorption, but not net hepatic glucose uptake or glycogen deposition, when glucose is given intraduodenally.

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.

Enhanced muscle glucose metabolism after exercise in the rat: the two phases

1984 ◽  
Vol 246 (6) ◽  
pp. E471-E475 ◽  
Author(s):  
L. P. Garetto ◽  
E. A. Richter ◽  
M. N. Goodman ◽  
N. B. Ruderman
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Phase I ◽  
Phase Ii ◽  
Muscle Glycogen ◽  
Glucose Utilization ◽  
Glycogen Synthesis ◽  
Moderate Intensity ◽  
Base Line ◽  
Two Phases

Thirty minutes after a treadmill run, glucose utilization and glycogen synthesis in perfused rat skeletal muscle are enhanced due to an increase in insulin sensitivity (Richter et al., J. Clin. Invest. 69: 785-793, 1982). The exercise used in these studies was of moderate intensity, and muscle glycogen was substantially repleted at the time (30 min postexercise) that glucose metabolism was examined. When rats were run at twice the previous rate (36 m/min), muscle glycogen was still substantially diminished 30 min after the run. At this time the previously noted increase in insulin sensitivity was still observed in perfused muscle; however, glucose utilization was also increased in the absence of added insulin (1.5 vs. 4.2 mumol X g-1 X h-1). In contrast 2.5 h after the run, muscle glycogen had returned to near preexercise values, and only the insulin-induced increase in glucose utilization was evident. The data suggest that the restoration of muscle glycogen after exercise occurs in two phases. In phase I, muscle glycogen is depleted and insulin-stimulated glucose utilization and glucose utilization in the absence of added insulin may both be enhanced. In phase II glycogen levels have returned to near base-line values and only the increase in insulin sensitivity persists. It is proposed that phase I corresponds to the period of rapid glycogen repletion that immediately follows exercise and phase II to the period of supercompensation.

scholarly journals The influence of insulin and of contraction on glucose metabolism in the perfused diaphragm muscle from normal and streptozotocin-treated rats

1971 ◽  
Vol 125 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Anne Beloff-Chain ◽  
E. B. Chain ◽  
K. A. Rookledge
Keyword(s):  
Glucose Metabolism ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Diaphragm Muscle ◽  
Co2 Production ◽  
Experimental Conditions ◽  
Contracting Muscle ◽  
Hexose Phosphate ◽  
Muscle Formation ◽  
Resting Muscle

1. The metabolism of [U-14C]glucose in perfused resting and contracting diaphragm muscle from normal rats and rats made diabetic with streptozotocin was studied in the presence and absence of insulin. 2. The incorporation of [U-14C]-glucose into glycogen and oligosaccharides was stimulated by insulin under all experimental conditions studied. 3. In the normal perfused resting diaphragm muscle the incorporation of radioactivity from [14C]glucose into lactate and CO2 was not affected by insulin. 4. Periodic contractions, induced by electrical stimulation of the perfused diaphragm muscle in the absence of insulin, caused an increased incorporation of 14C into glycogen and hexose phosphate esters, whereas incorporation of 14C into lactate was greatly decreased. Production of 14CO2 in the contracting muscle was not significantly different from that in resting muscle. Addition of insulin to the perfusion liquid caused a further increase in formation of [14C]-glycogen in contracting muscle to values reached in the resting muscle in the presence of insulin. Formation of [14C]lactate was also stimulated by insulin, to values close to those found in the resting muscle in the presence of insulin. 5. In the diabetic resting muscle the rate of glucose metabolism was very low in the absence of insulin. Insulin increased formation of [14C]glycogen to the value found in normal muscle in the absence of insulin. Production of 14CO2 and formation of [14C]hexose phosphate remained unchanged. 6. In the diabetic contracting muscle production of 14CO2 was increased to values approaching those found in normal contracting muscle. Formation of [14C]lactate and [14C]glycogen was also increased by contraction, to normal values. Only traces of [14C]hexose phosphate were detectable. Addition of insulin to the perfusion medium stimulated formation of [14C]glycogen, to values found in normal contracting muscle. Production of [14C]hexose phosphate was stimulated by insulin, to approximately the values found in the normal contracting muscle. Production of 14CO2 and [14C]lactate, however, was not significantly affected by insulin. 7. These results indicate that the defects of glucose metabolism observed in perfused resting diabetic diaphragm muscle can be partially corrected by contraction, and in the presence of insulin the contracting diabetic muscle has a completely normal pattern of glycogen synthesis and lactate production, but CO2 production remains impaired.

scholarly journals Histone deacetylase 5 regulates glucose uptake and insulin action in muscle cells

2012 ◽  
Vol 49 (3) ◽  
pp. 203-211 ◽  
Author(s):  
Suryaprakash Raichur ◽  
Song Hooi Teh ◽  
Kenji Ohwaki ◽  
Vidhi Gaur ◽  
Yun Chau Long ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Histone Deacetylases ◽  
Insulin Action ◽  
Metabolic Flux ◽  
Muscle Development ◽  
Glycogen Synthesis ◽  
Hdac Inhibitors ◽  
Muscle Cells ◽  
Histone Deacetylation

The class IIa histone deacetylases (HDACs) act as transcriptional repressors by altering chromatin structure through histone deacetylation. This family of enzymes regulates muscle development and phenotype, through regulation of muscle-specific genes including myogenin and MyoD (MYOD1). More recently, class IIa HDACs have been implicated in regulation of genes involved in glucose metabolism. However, the effects of HDAC5 on glucose metabolism and insulin action have not been directly assessed. Knockdown of HDAC5 in human primary muscle cells increased glucose uptake and was associated with increased GLUT4 (SLC2A4) expression and promoter activity but was associated with reduced GLUT1 (SLC2A1) expression. There was no change in PGC-1α (PPARGC1A) expression. The effects of HDAC5 knockdown on glucose metabolism were not due to alterations in the initiation of differentiation, as knockdown of HDAC5 after the onset of differentiation also resulted in increased glucose uptake and insulin-stimulated glycogen synthesis. These data show that inhibition of HDAC5 enhances metabolism and insulin action in muscle cells. As these processes in muscle are dysregulated in metabolic disease, HDAC inhibition could be an effective therapeutic strategy to improve muscle metabolism in these diseases. Therefore, we also examined the effects of the pan HDAC inhibitor, Scriptaid, on muscle cell metabolism. In myotubes, Scriptaid increased histone 3 acetylation, GLUT4 expression, glucose uptake and both oxidative and non-oxidative metabolic flux. Together, these data suggest that HDAC5 regulates muscle glucose metabolism and insulin action and that HDAC inhibitors can be used to modulate these parameters in muscle cells.

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