Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies indicate that intracellular insulin signalling involves the formation of reactive oxygen species (ROS) by NADPH oxidases (NOX). ROS inhibit intracellular protein tyrosin phosphatases whereby phosphoprotein signalling is enhanced and prolonged. We used the isolated perfused rat liver and detected ROS formation by measuring the surface fluorescence at wavelengths specific for the intracellular ROS sensor carboxydihydrodichlorofluorescein. Insulin (2, 5, 20 nM) induced low level ROS formation that was abolished by the NOX inhibitor diphenyleneiodonium chloride (4 microM). Studying insulin-dependent inhibition of glucagon-activated glucose production showed that melatonin (50 microM), used as ROS scavenger, inhibited ROS formation and blunted the effect of insulin on glucose production. The data support the general notion that hormone-dependent ROS formation modifies intracellular signal transduction.
 ...
PMID:Reactive oxygen species facilitate the insulin-dependent inhibition of glucagon-induced glucose production in the isolated perfused rat liver. 1899 75

During periods in which glucose absorption from the gastrointestinal (GI) tract is insufficient to meet body requirements, hepatic gluconeogenesis plays a key role to maintain normal blood glucose levels. The current studies investigated the role in this process played by vasodilatory-associated phosphoprotein (VASP), a protein that is phosphorylated in hepatocytes by cAMP/protein kinase A (PKA), a key mediator of the action of glucagon. We report that following stimulation of hepatocytes with 8Br-cAMP, phosphorylation of VASP preceded induction of genes encoding key gluconeogenic enzymes, glucose-6-phosphatase (G6p) and phosphoenolpyruvate carboxykinase (Pck1), and that VASP overexpression enhanced this gene induction. Conversely, hepatocytes from mice lacking VASP (Vasp-/-) displayed blunted induction of gluconeogenic enzymes in response to cAMP, and Vasp-/- mice exhibited both greater fasting hypoglycemia and blunted hepatic gluconeogenic enzyme gene expression in response to fasting in vivo. These effects of VASP deficiency were associated with reduced phosphorylation of both CREB (a key transcription factor for gluconeogenesis that lies downstream of PKA) and histone deacetylase 4 (HDAC4), a combination of effects that inhibit transcription of gluconeogenic genes. These data support a model in which VASP functions as a molecular bridge linking the two key signal transduction pathways governing hepatic gluconeogenic gene expression.
 ...
PMID:The role of vasodilator-stimulated phosphoprotein (VASP) in the control of hepatic gluconeogenic gene expression. 3101 43

Alcohol consumption during adolescence is known to cause different impairments in the hippocampus that could lead to persistent deficits in adulthood. A common pattern of alcohol use in adolescents consists of excessive and intermittent alcohol consumption over a very short period of time (binge drinking). Protein phosphorylation is a mechanism underlying memory processes and we have previously demonstrated changes in the rat hippocampal phosphoproteome after a single dose of ethanol; however, studies showing the phosphoprotein alterations in the hippocampus after repeated exposition to alcohol are limited. This study focuses on the identification of the phosphoproteins differentially regulated in the adolescent rat hippocampus after repeated ethanol administration by comparing different patterns of alcohol treatments according to dose and frequency of administration ((i) moderate dose-chronic use, (ii) low dose-intermittent use, and (iii) high dose-intermittent use). We have used a proteomic approach, including phosphoprotein enrichment by immobilized metal affinity chromatography, which revealed 21 proteins differentially affected depending on the pattern of alcohol treatment used. Many of these proteins are included in glycolysis and glucagon signaling pathways and are also involved in neurodegeneration, which could reinforce the role of metabolic alterations in the neural damage induced by repeated alcohol exposure during adolescence.
 ...
PMID:Effects of Intermittent versus Chronic-Moderate Ethanol Administration during Adolescence in the Adult Hippocampal Phosphoproteome. 3194 73


<< Previous 1 2