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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dynamics of glucose movement across perfused livers were assessed in carbon tetrachloride (CCl4)-injured rats. Rats were given CCl4 for 8 weeks and became glucose intolerant and hyperinsulinemic. The fasted rat liver was cyclically perfused with 4 mM lactate and various concentrations (0-20 mM) of glucose for 20 min. In the CCl4-injured liver, net glucose output was less suppressed at high glucose levels than in the normal liver (147 +/- 70 vs 18 +/- 10 mumol at 20 mM glucose, P < 0.05). Deposition of the carbon from [14C] glucose into glycogen was stimulated at high glucose levels and was markedly reduced in the CCl4-injured liver compared to the normal liver (0.58 +/- 0.33 mumol vs 1.44 +/- 0.20 mumol at 20 mM, P < 0.01). Conversion of [14C] lactate to [14C] glucose was not different between the CCl4-injured and the normal liver at each glucose level. Deposition of the carbon from [14C] acetate into glycogen in the CCl4-injured liver was larger than that in the normal liver at 0 mM glucose (0.81 +/- 0.15 mumol vs 0.32 +/- 0.06 mumol, P < 0.01), but was similar to the normal at 20 mM glucose. In the CCl4-injured liver, utilization of exogenous glucose was impaired at high glucose levels, and gluconeogenetic activity was not impaired at low glucose levels. These changes in the hepatic glucose metabolism seem to account for postprandial hyperglycemia without fasting hypoglycemia associated with liver diseases.
Biochem Mol Med 1995 Feb
PMID:Impaired glucose uptake and intact gluconeogenesis in perfused rat liver after carbon tetrachloride injury. 755 15

Expression of vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen and a potent angiogenic factor, is upregulated in response to a hypoxic or hypoglycemic stress. Here we show that the increase in steady-state levels of VEGF mRNA is partly due to transcriptional activation but mostly due to increase in mRNA stability. Both oxygen and glucose deficiencies result in extension of the VEGF mRNA half-life in a protein synthesis-dependent manner. Viewing VEGF as a stress-induced gene, we compared its mode of regulation with that of other stress-induced genes. Results showed that under nonstressed conditions, VEGF shares with the glucose transporter GLUT-1 a relatively short half-life (0.64 and 0.52 h, respectively), which is extended fourfold and more than eightfold, respectively, when cells are deprived of either oxygen or glucose. In contrast, the mRNAs of another hypoxia-inducible and hypoglycemia-inducible gene, grp78, as well as that of HSP70, were not stabilized by these metabolic insults. To show that VEGF and GLUT-1 are coinduced in differentially stressed microenvironments, multicell spheroids representing a clonal population of glioma cells in which each cell layer is differentially stressed were analyzed by in situ hybridization. Cellular microenvironments conducive to induction of VEGF and GLUT-1 were completely coincidental. These findings show that two different consequences of tissue ischemia, namely, hypoxia and glucose deprivation, induce VEGF and GLUT-1 expression by similar mechanisms. These proteins function, in turn, to satisfy the tissue needs through expanding its vasculature and improving its glucose utilization, respectively.
Mol Cell Biol 1995 Oct
PMID:Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes. 756 86

Induction of the 70 kDa heat shock protein (HSP70) by hypoxia and/or hypoglycemia and the effects of prior heat shock on injury owing to hypoxia and/or hypoglycemia were studied in rat cerebral endothelial cells. Hypoxia and/or hypoglycemia treatment resulted in increased expression of HSP70 only when such treatment was sufficient to cause detectable injury and when the initial treatment was followed by exposure of the cells to 24 h of normoxia and normoglycemia. Heat shock induced 24 h prior to treatment with 48 h of hypoxia slightly reduced endothelial cell damage as measured by fraction of lactate dehydrogenase release (10% decrease in injury). There was a more dramatic effect of prior heat shock on the moderate damage produced by 12 h of combined hypoxia and hypoglycemia (45% decrease), whereas the severe damage produced by 24 h of hypoxia and hypoglycemia was decreased by prior heat shock by only 16%. These results indicate that the hypoxia and hypoglycemia occurring in conjunction with ischemia are more likely to result in heat shock protein expression when there is injury to the tissue. Furthermore, heat shock protects cerebral endothelial cells from hypoxia and hypoglycemia either by slowing the initial development of injury or by delaying the onset of injury.
Mol Chem Neuropathol
PMID:Amelioration of hypoxic and hypoglycemic damage to cerebral endothelial cells. Effects of heat shock pretreatment. 763 16

A gene for autosomal recessive familial hyperinsulinism (HI) (OMIM: 256450), a neonatal metabolic disease characterized by inappropriate insulin secretion in the presence of severe hypoglycemia, was recently mapped to a 6.6 cM interval between the markers D11S926 and D11S928 on chromosome 11p in 15 families (1). In the current study we evaluated six additional families and five new markers, and further localized the gene between D11S419 and D11S1310. Using genotype data from CEPH Version 7 and data generated from this study, this region was estimated to be 0.8 cM in length. Significant linkage disequilibrium between markers and the HI gene was observed over a region of 10.3 cM (11 pter-D11S926-D11S1308-11pcen) for Ashkenazi Jewish chromosomes. Haplotype analysis showed that 12 of 36 HI chromosomes, versus one of 36 non-HI chromosomes, bore a specific haplotype for D11S419-D11S902-D11S921 (p < 0.0007), strongly suggesting a founder effect in this ethnic group.
Hum Mol Genet 1995 May
PMID:Recombinant mapping of the familial hyperinsulinism gene to an 0.8 cM region on chromosome 11p15.1 and demonstration of a founder effect in Ashkenazi Jews. 763 48

Malignant mesothelioma (MM) is an asbestos-associated cancer that is increasing in incidence worldwide and is refractory to conventional therapy. MM cells are potent sources of a number of cytokines, some of which have recently been shown to be directly involved in the aggressive growth and spread of MM tumors. Emerging data also suggest involvement of MM-derived cytokines in systemic paraneoplastic syndromes including immunosuppression, thrombocytosis, cachexia, amyloidosis, and hypoglycemia. Additional characterization of the expression of cytokines and cytokine receptors in situ in MM tumors may provide a more complete picture of the autocrine and paracrine processes which occur in MM. Improved therapy of MM, particularly cytokine-based approaches, is likely to benefit from further elucidation of the patterns and regulation of cytokine expression associated with MM tumors.
Am J Respir Cell Mol Biol 1995 May
PMID:The role of growth factors and cytokines in the tumorigenesis and immunobiology of malignant mesothelioma. 774 9

The regulation of ACTH secretion during stress is a multifactorial process that mainly involves two hypothalamic neurohormones: corticotrophin-releasing factor (CRF) and arginine vasopressin (AVP). In this report we measured, using semiquantitative in situ hybridization, the concentrations of CRF and AVP mRNA in hypophyseotrophic paraventricular parvocellular cell bodies of male rats after an acute (3-h) exposure to insulin-induced hypoglycaemia. Insulin injection (2.5 IU/kg) induced a significant decrease in blood glucose levels and a strong increase in plasma ACTH concentrations. The concentration of CRF mRNA in the paraventricular nucleus (PVN) was significantly increased after insulin-induced hypoglycaemia (150% of control levels), while the number of CRF mRNA-containing cell bodies was not changed. Double-labelling experiments demonstrated that the number of CRF mRNA-containing cell bodies that also contained AVP mRNA was doubled after insulin injection. These data demonstrate that the established increased colocalization of AVP immunoreactivity in nerve terminals immunoreactive for CRF after exposure to stress follows a pretranslational activation of AVP synthesis. Cell-by-cell analysis indicated that the mean CRF hybridization signal was increased in double-labelled cells (about 150% of control levels), suggesting that the increase in CRF gene expression occurs equally in the AVP-synthesizing and in the AVP-deficient CRF mRNA-containing cell bodies. The mean AVP hybridization signal in the double-labelled cells was decreased, suggesting that the amount of AVP mRNA was unchanged in the cell bodies that expressed both CRF and AVP in the basal state and that AVP mRNA levels in the cell bodies recruited after insulin-induced hypoglycaemia were below control values.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Endocrinol 1994 Dec
PMID:Insulin-induced hypoglycaemia increases colocalization of corticotrophin-releasing factor and arginine vasopressin mRNAs in the rat hypothalamic paraventricular nucleus. 789 49

The effect of insulin induced hypoglycemia was studied on the activities of Acetylcholinesterase (AChE) which hydrolizes acetylcholine (ACh) and Na+, K(+)-ATPase, the enzymatic version of Na+,K(+)-pump from rat heart, liver and kidney. AChE activity was decreased significantly from two subcellular fractions of all the three tissues after 1,2 and 3 hours of insulin administration (5 units/100 gm body weight) Na+, K(+)-ATPase activity was decreased in liver and kidney, whereas, a significant increase in heart ATPase activity was observed. Blood glucose level was significantly lower than control values after 1, 2 and 3 hours of insulin injection, and the protein content from these tissues did not show any significant change under this physiological stress.
Biochem Mol Biol Int 1993 Nov
PMID:Effect of insulin induced hypoglycemia on acetylcholinesterase and Na+, K(+)-ATPase activity of rat heart, liver and kidney. 811 15

The activities of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7), responsible for hydrolysis of acetylcholine and Na+,K(+)-ATPase (Mg(2+)-dependent ATP phosphohydrolase, EC 3.6.1.3), which plays a crucial role in neurotransmission, were determined in four brain regions after 1, 2, and 3 h of insulin administration. Significant decrease in the acetylcholinesterase and Na+,K(+)-ATPase activities was observed in the soluble and total particulate fractions from cerebral hemispheres, cerebellum, brain stem, and diencephalon + basal ganglia after 1, 2, and 3 h of insulin-induced hypoglycemia. Blood glucose level decreased significantly after 1 h of insulin administration and remained at low level for 2 h thereafter, whereas, the protein content in different subcellular fractions from four brain regions did not show any significant change under this physiological stress.
Mol Chem Neuropathol 1994 Jan
PMID:Acetylcholinesterase and Na+,K(+)-ATPase activities in different regions of rat brain during insulin-induced hypoglycemia. 817 74

The effect of incubation with the protein kinase C activator, 4 beta-phorbol 12,13-dibutyrate (beta-PDBu) on the electrophysiological responses to hypoxia and combined hypoxia and hypoglycemia was investigated in the rat hippocampal slice. Preincubation with beta-PDBu prevents adenosine-mediated inhibition of synaptic transmission under normoxic, normoglycemic conditions. beta-PDBu preincubation also reduces the adenosine-mediated hypoxia-induced depression of synaptic transmission revealing a substantial adenosine-independent hypoxia-induced depression of synaptic transmission. During combined hypoxia and hypoglycemia, slices preincubated in beta-PDBu display a significant shortening of the time of anoxic depolarization, an effect of beta-PDBu that is not mimicked by application of the adenosine antagonist cyclopentyltheophylline (8-CPT). It is concluded that the state of PKC activation may influence the electrophysiological responses to hypoxia and ischemia.
Mol Chem Neuropathol 1995 Sep
PMID:Phorbol ester alters the electrophysiological responses to hypoxia and ischemic-like conditions in the rat hippocampal slice. 858 22

We investigated the effect of hypoglycemic treatment on the activation of the AP-1 transcription factors and the regulation of basic fibroblast growth factor (bFGF) gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells. Northern blot and gel mobility shift assays showed that hypoglycemic treatment induced c-jun and c-fos gene expression, AP-1 binding activity, as well as bFGF gene expression. Moreover, transfected cells expressing high levels of abnormal c-Jun protein exhibited a reduction in the bFGF protein levels compared to parental cells. A potent protein kinase C (PKC) inhibitor, H-7 (60 micrograms/ml) suppressed the stress-induced bFGF gene expression. Our study also demonstrated that H-7 did not facilitate the decay of bFGF mRNA. Thus, the suppression of bFGF gene expression by treatment with H-7 was due to the effect of the drug on the synthesis of bFGF mRNA rather than the stability of bFGF mRNA. Our data suggest that hypoglycemia-induced bFGF gene expression is mediated through the activation of PKC and the AP-1 transcription factors.
Mol Cell Biochem 1996 Feb 23
PMID:Hypoglycemia-induced AP-1 transcription factor and basic fibroblast growth factor gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells. 870 Jan 61


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