Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Starvation (48 h) decreased the concentration of mRNA of the insulin-responsive glucose transporter isoform (GLUT 4) in interscapular brown adipose tissue (IBAT) (56%) and tibialis anterior (10%). Despite dramatic [7-fold (tibialis anterior) and 40-fold (IBAT)] increases in glucose utilization after 2 and 4 h of chow re-feeding, no significant changes in GLUT 4 mRNA concentration were observed in these tissues over this re-feeding period. The results exclude changes in GLUT 4 mRNA concentration in mediating the responses of glucose transport in these tissues to acute re-feeding after prolonged starvation.
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PMID:Glucose transporter expression and glucose utilization in skeletal muscle and brown adipose tissue during starvation and re-feeding. 137 67

Starvation (48 h) decreases fructose 2,6-bisphosphate (Fru-2,6-P2) concentrations and the ratio of free to acylated carnitine in hearts of euthyroid rats. These decreases, which are indicative of increased lipid fuel oxidation, are accompanied by decreased rates of glucose uptake and phosphorylation, assessed by using radioactive 2-deoxyglucose. Cardiac concentrations of acylated carnitines were increased at the expense of free carnitine even in the fed state in response to experimental hyperthyroidism, but neither Fru-2,6-P2 concentrations nor rates of glucose utilization were suppressed. Starvation (48 h) did not further increase the proportion of acylated carnitine in the heart in hyperthyroidism, and suppression of Fru-2,6-P2 concentrations and glucose utilization rates by starvation was attenuated. Although glucose utilization rates were decreased, starvation did not decrease immunoreactive GLUT 4 protein concentrations. Furthermore, although hyperthyroidism was associated with a statistically significant (30-40%) increase in relative abundance of GLUT 4 mRNA, the amount of GLUT 4 protein was not increased by hyperthyroidism in either the fed or the starved state. The results demonstrate a significant effect of hyperthyroidism to enhance cardiac glucose utilization in starvation by a mechanism which does not involve changes in GLUT 4 expression but may be secondary to changes in glucose-lipid interactions at the tissue level.
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PMID:Mechanisms regulating cardiac fuel selection in hyperthyroidism. 153 May 84

Glucose uptake by adipose tissue is mediated by two glucose transporters: GLUT4, which is most abundant, and GLUT1. While GLUT1 is expressed in many tissues, GLUT4 is unique to tissues that exhibit insulin-stimulated glucose uptake (heart and skeletal muscle and adipose tissue). In the diabetic state and during starvation, insulin-stimulated glucose uptake and GLUT4 expression are decreased in tissue adipocytes. Using 3T3-L1 adipocytes in culture, we investigated the possibility that these effects are mediated by elevated cellular cAMP. When 3T3-L1 adipocytes were treated for 16 hr with forskolin or 8-Br-cAMP, GLUT4 mRNA and protein were decreased by approximately 70%, while expression of GLUT1 mRNA and protein was increased 3-fold. These changes were accompanied by an increased basal rate of 2-deoxyglucose uptake and a loss of acute responsiveness of hexose uptake to insulin. The magnitude of GLUT4 mRNA depletion/GLUT1 mRNA accumulation was dependent upon the concentration of 8-Br-cAMP. The decrease of GLUT4 mRNA caused by 8-Br-cAMP was the result of a decreased transcription rate, while the half-life of the message was unaffected. The increase in GLUT1 mRNA caused by 8-Br-cAMP was the result of both transient transcriptional activation and mRNA stabilization. We suggest that down-regulation of GLUT4 mRNA in adipose tissue in the diabetic state and during starvation is the result of repression of transcription of the GLUT4 gene caused by cAMP.
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PMID:Transcriptional repression of the mouse insulin-responsive glucose transporter (GLUT4) gene by cAMP. 170 11

The basic characteristics of hexose uptake and regulation of the glucose transporter (GLUT1) by D-glucose and insulin were studied in primary cultures of bovine brain microvessel endothelial cells (BMECs). A non-metabolizable glucose analog, 3-O-[3H]methyl-D-glucose [( 3H]3MG), was used as a model substrate, and the uptake was studied using BMECs grown in tissue culture plates. Uptake of [3H]3MG was equilibrative, temperature-dependent, and independent of sodium. The uptake also decreased gradually with culture age from 7 to 13 days. Saturation kinetics were observed for [3H]3MG uptake and the apparent Km and Vmax values were determined to be 13.2 mM and 169 nmol/mg per min, respectively. Pre-incubation with high concentrations of D-glucose and 3MG accelerated [3H]3MG uptake by BMECs by a counter-transport mechanism. D-Glucose, 2-deoxy-D-glucose, D-mannose, D-xylose, D-galactose and D-ribose showed significant competitive inhibition with [3H]3MG, whereas L-glucose, D-fructose, and sucrose did not affect [3H]3MG uptake by BMECs. [3H]3MG uptake was inhibited significantly by cytochalasin B and phloretin but not by phlorizin, 2,4-dinitrophenol, or ouabain. D-Glucose starvation of BMECs by incubation with D-glucose-free media for 24 h resulted in a significant increase (40-70%) in uptake of [3H]3MG compared with control conditions (7.3 mM D-glucose). Low D-glucose treatments (2.43 and 1.83 mM) for 7 days induced a slight but significant increase (20%) in [3H]3MG uptake, while long-term high glucose treatments (25 mM) showed no significant effect on [3H]3MG uptake irrespective of exposure time. The increase in [3H]3MG accumulation following D-glucose starvation was dependent upon starvation time (12 to 48 hr) and protein synthesis. Refeeding of D-glucose (7.3 mM) to D-glucose-starved BMECs resulted in a return of [3H]3MG uptake to control levels in 48 h. The D-glucose-starvation-induced increase in [3H]3MG uptake was shown to result from an increase in Vmax; the Km remained constant. In addition, D-glucose-starved BMECs were shown to have an increased level of GLUT1 using an antibody against human GLUT1 and an enzyme-linked immunosorbent assay (ELISA). The increased uptake following D-glucose starvation was not significantly affected by the presence of L-glucose, was partially impaired by the presence of D-galactose, D-fructose, and D-xylose, and was completely inhibited by the presence of D-mannose and 3MG. Furthermore, preincubation of BMECs with insulin (10 micrograms/ml) for 20 min did not affect the uptake of [3H]3MG or 2-deoxy-D-[3H]glucose ([3H]2DG).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hexose uptake in primary cultures of bovine brain microvessel endothelial cells. I. Basic characteristics and effects of D-glucose and insulin. 175 15

A new method for photoaffinity labeling of glucose transporters has been used to compare the effects of glucose-starvation, acute-insulin, and chronic-insulin treatments on the cell-surface glucose transporters in 3T3-L1 adipocytes. Starvation alone increased the cell-surface levels of GLUT1 and GLUT4 by approximately 4- and approximately 2-fold, respectively. As shown by Calderhead, D, M., Kitagawa, K., Tanner, L.T., Holman, G.D., and Lienhard, G.E. (1990) J. Biol. Chem. 265, 13800-13808) acute-insulin treatment increased cell-surface GLUT1 and GLUT4 by approximately 5- and approximately 15-fold respectively. In contrast to this, chronic-insulin treatment gave a further 3-4-fold increase in both cell-surface and total cellular GLUT1, but availability of GLUT4 at the cell-surface was down-regulated to half the level found in the acute treatment but with no change in the total cellular level. This effect occurred in starved and non-starved cells and suggests that starvation, acute-insulin, and chronic-insulin treatments regulate glucose transporter availability through independent mechanisms. The down-regulation of GLUT4 reached a maximally reduced cell-surface level in 6 h while the rise in GLUT1 reached a maximum after 24-48 h. The rise in GLUT1 appeared to compensate for the decline in cell-surface GLUT4 as glucose transport activity was further increased during the long term treatment with insulin. The down-regulation of GLUT4 due to the chronic-insulin treatment is associated with a marked resistance of the cells to restimulate glucose transport and particularly to recruit further GLUT4 to the cell-surface following an additional insulin treatment. The defect appears to be in the signaling mechanism that is responsible for translocation.
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PMID:Chronic treatment with insulin selectively down-regulates cell-surface GLUT4 glucose transporters in 3T3-L1 adipocytes. 205 Jun 74

Glucose transport in 3T3L1 adipocytes is mediated by two facilitated diffusion transport systems. We examined the effect of chronic glucose deprivation on transport activity and on the expression of the HepG2 (GLUT 1) and adipocyte/muscle (GLUT 4) glucose transporter gene products in this insulin-sensitive cell line. Glucose deprivation resulted in a maximal increase in 2-deoxyglucose uptake of 3.6-fold by 24 h. Transport activity declined thereafter but was still 2.4-fold greater than the control by 72 h. GLUT 1 mRNA and protein increased progressively during starvation to values respectively 2.4- and 7.0-fold greater than the control by 72 h. Much of the increase in total immunoreactive GLUT 1 protein observed later in starvation was the result of the accumulation of a non-functional or mistargeted 38 kDa polypeptide. Immunofluorescence microscopy indicated that increases in GLUT 1 protein occurred in presumptive plasma membrane (PM) and Golgi-like compartments during prolonged starvation. The steady-state level of GLUT 4 protein did not change during 72 h of glucose deprivation despite a greater than 10-fold decrease in the mRNA. Subcellular fractionation experiments indicated that the increased transport activity observed after 24 h of starvation was principally the result of an increase in the 45-50 kDa GLUT 1 transporter protein in the PM. The level of the GLUT 1 transporter in the PM and low-density microsomes (LDM) was increased by 3.9- and 1.4-fold respectively, and the GLUT 4 transporter content of the PM and LDM was 1.7- and 0.6-fold respectively greater than that of the control after 24 h of glucose deprivation. These data indicate that newly synthesized GLUT 1 transporters are selectively shuttled to the PM and that GLUT 4 transporters undergo translocation from an intracellular compartment to the PM during 24 h of glucose starvation. Thus glucose starvation results in an increase in glucose transport in 3T3L1 adipocytes via a complex series of events involving increased biosynthesis, decreased turnover and subcellular redistribution of transporter proteins.
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PMID:Differential regulation of the HepG2 and adipocyte/muscle glucose transporters in 3T3L1 adipocytes. Effect of chronic glucose deprivation. 222 13

The product of the c-myc proto-oncogene (c-Myc) is involved in the control of cell proliferation, differentiation, and apoptosis. It acts as a transcription factor that recognizes the CACGTG motif. This sequence has also been found in the glucose-responsive elements of genes involved in the control of liver glycolysis and lipogenesis. To determine whether c-Myc can regulate hepatic carbohydrate metabolism in vivo, transgenic mice that overexpress c-myc under control of the P-enolpyruvate carboxykinase (PEPCK) gene promoter have been generated. These mice showed a threefold increase in c-Myc protein in liver nuclei. Hepatocytes from transgenic mice were normal and did not acquire the fetal phenotype. However, transgenic mice showed higher levels (threefold) of L-type pyruvate kinase mRNA and enzyme activity than control mice. The increase in pyruvate kinase activity led to a three- to fivefold increase in liver lactate content and a fivefold induction of lactate production by hepatocytes in primary culture. The expression of the 6-phosphofructo-2-kinase gene was also increased in the liver of these transgenic mice. The induction of hepatic glycolysis was related with an increase in the expression (about fourfold) and activity (about threefold) of liver glucokinase, whereas no change was noted in hexokinase-I. This change in glucokinase activity led to an increase in both glucose 6-phosphate and glycogen contents in the liver of transgenic mice. The expression of the liver-specific glucose transporter GLUT2 was also increased in transgenic mice, whereas no change was noted in the mRNA concentration of GLUT1. Furthermore, the changes of liver glucose metabolism led to a marked reduction of blood glucose (25%) and insulin (40%) concentrations in starvation, whereas the fall in both was only 10% in fed mice. Thus, liver glucose metabolism could determine the blood glucose and insulin set points in the transgenic mice. All these results indicated that the increase in c-Myc protein was able to induce liver glucose utilization and accumulation, and suggested that c-Myc transcription factor is involved in the control in vivo of liver carbohydrate metabolism.
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PMID:Evidence from transgenic mice that myc regulates hepatic glycolysis. 764 6

Elevated glucose transport rates during glucose deprivation are phenomena that have been observed in several different types of cells in culture. We show here that glucose transport rates in 3T3-L1 adipocytes increased by 10-fold within 18 h in response to glucose deprivation, confirming earlier work by Van Putten and Krans (Van Putten, J. P. M., and Krans, H. M. J. (1985) J. Biol. Chem. 260, 7996-8001). Mannose and 3-O-methylglucose (a nonmetabolizable glucose analog), but not fructose or galactose, blocked the increase in transport activity. Although the increase in transport was dependent on new protein synthesis, only a small and transient increase in GLUT 1 mRNA (less than 2-fold) was observed. In addition, the level of the normal isoform of GLUT 1 (46 kDa) did not increase. A lower molecular mass isoform (37 kDa) was observed but not until 15 h after glucose removal, the appearance of which was clearly not correlated with the increase in activity. Further, the extracellular glucose concentration required to elicit accumulation of this form (p37) was 2 orders of magnitude less than that required for transport stimulation (5 microM versus 500 microM glucose; p37 accumulation and transport activation, respectively). Interestingly, p37 was seen in the presence of galactose, but not fructose, despite elevated transport activity with either sugar. The p37 isoform was slightly larger than N-glycosidase F-treated GLUT 1 (36 kDa), implying that this form is still glycosylated, albeit incompletely. It is not known if p37 is functional, but the time- and sugar-dependent appearance of the lower isoform suggests that p37 is not responsible for starvation-induced transport but potentially represents an underglycosylated precursor of the normal, 46-kDa isoform of GLUT 1.
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PMID:Effect of glucose deprivation of GLUT 1 expression in 3T3-L1 adipocytes. 767 53

Rat L6 myoblasts were recently shown to possess the GLUT 1, 3 and 4 transporters, and not the GLUT 2 isoform [1]. This investigation examined the expression and properties of the GLUT 1 isoform. GLUT 1 transcript level was significantly reduced in cells grown at high densities and during myogenic differentiation. A comparison of the GLUT 1 and 4 transcript levels in myogenesis-competent and impaired cells revealed an inverse relationship between these two isoforms. This relationship was confirmed by studies using two independent spontaneous GLUT 3- GLUT 4- mutants, M1 and M3. These mutants possessed very high level of the GLUT 1 isoform, but negligible amount of the GLUT 3 and 4 isoforms. GLUT 1 expression was also subject to positive regulation. Glucose starvation was found to increase not only the levels of the GLUT 1 transcript and transporter, but also the intrinsic activity of the GLUT 1 transporter. Studies with M1 and M3 mutants revealed that the GLUT 1 transporter was not functional in glucose-grown cells, even though it was present at a very high level in the plasma membrane. This transporter became functional when cells were starved for glucose. The functional GLUT 1 transporter had an apparent Km value of around 0.9 mM, and was sensitive to cytochalasin B, phloretin, phlorizin and pCMBS.
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PMID:Use of hexose transport mutants to examine the expression and properties of the rat myoblast GLUT 1 transport process. 769 90

The erythrocyte (or HepG2/brain) type glucose transporter (GLUT 1) was the first of the family of facilitative glucose transporter proteins to be cloned [M. Mueckler et al., Science 229, 941-945, 1985]. GLUT 1 is expressed in most tissue types, all cell lines, transformed cells and tumour cells. It is thought to be responsible for "housekeeping" levels of glucose transport, i.e. the uptake of glucose required for oxidative phosphorylation. The rate of glucose transport via GLUT 1 can be regulated under conditions in which the metabolic rate must be adjusted such as cell division (mitosis and meiosis), differentiation, transformation and nutrient starvation. Here we review the recent literature on the control of glucose transport of mitogens, growth factors and oncogenes, and discuss some of the implications for the integration of cellular signalling pathways and cell growth.
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PMID:Growth factors, mitogens, oncogenes and the regulation of glucose transport. 813 71


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