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

Chick liver cell monolayers synthesize fatty acids at in vivo rates and are responsive to insulin and glucagon. High rates of fatty acid synthesis are maintained with insulin present and lost slowly without insulin. Glucagon or 3',5'-cyclic AMP cause immediate cessation of fatty acid synthesis. The site of inhibition appears to be cytoplasmic acetyl-CoA carboxylase which catalyzes the first committed step of fatty acid synthesis. Liver carboxylase exists either as catalytically inactive protomers or active filamentous polymers. Citrate, an allosteric activator of the enzyme, is required for both catalysis and polymerization. Glucagon and cAMP cause an immediate decrease in the cytoplasmic citrate concentration of chick liver cells apparently by inhibiting the conversion of glucose to citrate at the phosphofructokinase reaction. Since fatty acid synthesis and citrate level are closely correlated, citrate appears to be a feed-forward activator of the carboxylase in vivo. Compelling evidence indicates that carboxylase filaments are present in the intact cell when citrate levels are high and depolymerize when citrate levels fall. Hence, carboxylase activity and fatty acid synthetic rate appear to be determined by cytoplasmic citrate level.
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PMID:Hormonal regulation of acetyl-CoA carboxylase activity in the liver cell. 4 83

The hypothesis that the anxiety induced by repeated injections affects brain energy metabolism was tested. Normal 19- to 21-day-old mice were stressed by two sham intraperitoneal injections within 4 min, at which time they were decapitated. Noninjected, control littermates were quickly decapitated. Momentary stress increased plasma glucose (12%), glycerol (85%), beta-hydroxybutyrate (108%), and lactate (153%)--a reflection of elevated plasma cortisol (25%) and glucagon (45%). In brain, stress increased levels of glucose-6-P (15%) and fructose-6-P (17%). The brain pyruvate concentration increased 74%; lactate 76%. Citrate, alpha-ketoglutarate, and malate increased 15, 95, and 37%, respectively. Levels of glycogen, glucose, phosphocreatine, ATP, ADP, and AMP were unchanged. The brain lactate/pyruvate ratio was normal but the brain/plasma lactate ratio fell 32%. Metabolite changes in the stressed animals were compatible with a decrease in the glycolytic flux at the phosphofructokinase step and a paradoxical increased flux in the Krebs citric acid cycle. The decreased brain/plasma lactate ratio supported increased uptake of lactate from plasma and increased brain lactate oxidation. Metabolite changes similar to those described above occurred in unstressed mice injected with lactate. Findings confirm a positive effect of stress on brain metabolism, support a role for lactate as an oxidative fuel for brain, and caution that the rate of cerebral glucose utilization may not always reflect brain energy (oxidative) metabolism accurately.
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PMID:Effect of momentary stress on brain energy metabolism in weanling mice: apparent use of lactate as cerebral metabolic fuel concomitant with a decrease in brain glucose utilization. 279 72

The short-term regulation of rat liver acetyl-CoA carboxylase by glucagon has been studied in hepatocytes from rats that had been fasted and refed a fat-free diet. Glucagon inhibition of the activity of this enzyme can be accounted for by a direct correlation between phosphorylation, polymer-protomer ratio, and activity. Glucagon rapidly inactivates acetyl-CoA carboxylase with an accompanying 4-fold increase in the phosphorylation of the enzyme and 3-fold increase in the protomer-polymer ratio of enzyme protein. Citrate, an allosteric activator of acetyl-CoA carboxylase required for enzyme activity, has no effect on these phenomena, indicating a mechanism that is independent of citrate concentration within the cell. The observation of these effects of glucagon on acetyl-CoA carboxylase activity is absolutely dependent upon the minimization of proteolytic degradation of the enzyme after cell lysis. Therefore, for the first time, an interrelationship has been demonstrated between phosphorylation, protomer-polymer ratio, and citrate for the inactivation of acetyl-CoA carboxylase by glucagon.
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PMID:Mechanism of glucagon inhibition of liver acetyl-CoA carboxylase. Interrelationship of the effects of phosphorylation, polymer-protomer transition, and citrate on enzyme activity. 285 22

1. The effect of oleate on the subcellular distribution of ATP, 2-oxoglutarate, glutamate, citrate, malate and phosphoenolpyruvate was studied in hepatocytes from rats starved for 48 h by applying a modified digitonin method. The results markedly differ from those observed after glucagon [Siess, E. A., Brocks, D. G., Lattke, H. K., and Wieland, O. H. (1977) Biochem J. 166, 225-235]. Total cellular amounts and the distribution of ATP and 2-oxoglutarate remained unchanged. In the mitochondrial matrix glutamate was increased, while mitochondrial phospho-enolpyruvate was decreased. Citrate and malate were increased both in the mitochondrial and cytosolic space. 2. In contrast to the effect of glucagon, gluconeogenesis from dihydroxyacetone, fructose or glutamine was not stimulated by oleate. Gluconeogenesis from propionate was even inhibited by the fatty acid. 3. The stimulation by glucagon of glucose production from dihydroxyacetone or fructose was undiminished in biotin-deficient hepatocytes. Glucose formation from lactate, however, was stimulated only in biotin-substituted hepatocytes. 4. The results indicate that oleate stimulates gluconeogenesis by increasing pyruvate carboxylase activity (EC 6.4.1.1), whereas glucagon displays a more complex mode of action.
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PMID:Distinctive roles of oleate and glucagen in gluconeogenesis. 746 Sep 51

Long term feeding a sucrose-rich diet (SRD) to normal Wistar rats led to multiphasic changes in the activity of the pyruvate dehydrogenase complex (PDH), characterized by a significant decrease in PDHa (active form) in the short term on SRD (3 weeks) when compared to control rats fed the standard chow (STD). Although PDHa returned spontaneously to control values in the medium term (6-8 weeks) on SRD, an even more pronounced decrease was recorded when rats were kept long term on the SRD (15 weeks). Low PDHa levels recorded in the short and long term were accompanied by a two fold increase in heart acetyl-CoA concentration and the acetyl-CoA/CoASH ratio. Tissue long-chain acyl-CoA and triacylglycerol levels were also significantly higher in SRD fed rats. Spontaneous normalization of all the above metabolic parameters was observed during the medium term on SRD. Glucose-6-phosphate levels remained within control values during the short and medium term, in contrast to a two fold increase recorded in the long term on SRD. Glycogen concentrations were found moderately elevated only in the long term. Citrate concentrations were slightly increased in the short and greatly in the long term, and the fructose-2,6-bisphosphate/citrate ratio was found significantly decreased only during the long term on SRD. After 3 weeks on SRD, the protal vein Insulin/Glucagon (I/G) molar ratio was three times higher in SRD than STD rats, as opposed to an unchanged I/G ratio found in the long term.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiphasic metabolic changes in the heart of rats fed a sucrose-rich diet. 783 21

K cells are a subpopulation of enteroendocrine cells that secrete glucose-dependent insulinotropic polypeptide (GIP), a hormone that promotes glucose homeostasis and obesity. Therefore, it is important to understand how GIP secretion is regulated. GIP-producing (GIP/Ins) cell lines secreted hormones in response to many GIP secretagogues except glucose. In contrast, glyceraldehyde and methyl pyruvate stimulated hormone release. Measurements of intracellular glucose 6-phosphate, fructose 1,6-bisphosphate, and pyruvate levels, as well as glycolytic flux, in glucose-stimulated GIP/Ins cells indicated that glycolysis was not impaired. Analogous results were obtained using glucose-responsive MIN6 insulinoma cells. Citrate levels increased similarly in glucose-treated MIN6 and GIP/Ins cells. Thus pyruvate entered the tricarboxylic acid cycle. Glucose and methyl pyruvate stimulated 1.4- and 1.6-fold increases, respectively, in the ATP-to-ADP ratio in GIP/Ins cells. Glyceraldehyde profoundly reduced, rather than increased, ATP/ADP. Thus nutrient-regulated secretion is independent of the ATP-dependent potassium (K(ATP)) channel. Antibody staining of mouse intestine demonstrated that enteroendocrine cells producing GIP, glucagon-like peptide-1, CCK, or somatostatin do not express detectable levels of inwardly rectifying potassium (Kir) 6.1 or Kir 6.2, indicating that release of these hormones in vivo may also be K(ATP) channel independent. Conversely, nearly all cells expressing chromogranin A or substance P and approximately 50% of the cells expressing secretin or serotonin exhibited Kir 6.2 staining. Compounds that activate calcium mobilization were potent secretagogues for GIP/Ins cells. Secretion was only partially inhibited by verapamil, suggesting that calcium mobilization from intracellular and extracellular sources, independent from K(ATP) channels, regulates secretion from some, but not all, subpopulations of enteroendocrine cells.
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PMID:Studies with GIP/Ins cells indicate secretion by gut K cells is KATP channel independent. 1267 50