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)

Avian lipogenesis was studied in the chicken hepatocarcinoma LMH cell line. The differentiated and lipogenic status of these cells was evidenced by the presence of the albumin mRNA as well as of some mRNA coding for enzymes involved in lipogenesis (acetyl-CoA carboxylase, fatty acid synthase, delta 9 desaturase) and for apoproteins (apoprotein B and A1). These results were further confirmed by the analysis of triglyceride synthesis and secretion rates in growing cells. A time course analysis showed that triglyceride metabolism was affected by cell density. Hormone responsiveness of triglyceride production was also analyzed. Insulin, triiodothyronine and glucagon to a lesser extent were shown to regulate lipogenesis of LMH cells. The results were compared with those obtained in primary cultures of chicken hepatocytes.
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PMID:Triglyceride synthesis and secretion and lipogenesis implicated gene expression in the chicken hepatocarcinoma cell line LMH. 940 72

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the first committed step in hepatic gluconeogenesis. Glucagon and glucocorticoids stimulate PEPCK gene transcription, whereas insulin has a dominant inhibitory effect. We have shown that inhibitors of 1-phosphatidylinositol 3-kinase (PI 3-kinase) block this action of insulin. In contrast, three distinct agents, all of which prevent activation of p42/p44 mitogen-activated protein (MAP) kinase, have no effect on the regulation of PEPCK transcription by insulin. However, a subsequent report has suggested that this pathway is involved in the inhibition of cAMP-induced PEPCK gene transcription by insulin. To address these conflicting data, we re-examined the Ras MAP kinase pathway, not only with respect to regulation of PEPCK gene transcription, but also for regulation of PI 3-kinase and p42/p44 MAP kinase. Overexpression of constitutively active Ras (V61) (or Raf-1 (RafCAAX)) partially represses PEPCK transcription in hepatoma cells. However, an inhibitor of MAP kinase kinase blocks this action of RafCAAX but has no effect on regulation of PEPCK gene transcription by insulin. Second, the action of a dominant negative Ras (N17Ras) on PEPCK gene transcription correlates more closely with the inhibition of PI 3-kinase than with the inhibition of p42/p44 MAP kinase. Third, insulin cannot activate p42/p44 MAP kinase in the presence of cAMP even though cAMP-induced PEPCK gene transcription is inhibited by insulin. This data confirms that the Ras MAP kinase pathway is not required for the regulation of PEPCK gene transcription by insulin and demonstrates the importance of employing multiple techniques when investigating the function of signaling pathways.
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PMID:Activation of the ras mitogen-activated protein kinase-ribosomal protein kinase pathway is not required for the repression of phosphoenolpyruvate carboxykinase gene transcription by insulin. 945 31

Insulin-like effects of glucagon-like peptide-1(7-36)amide (GLP-1) in rat liver, skeletal muscle and fat, and also the presence of GLP-1 receptors in these extrapancreatic tissues, have been documented. In skeletal muscle and liver, the action of GLP-1 is not associated with an activation of adenylate cyclase, and in cultured murine myocytes and hepatoma cell lines, it was found that GLP-1 provokes the generation of inositolphosphoglycan molecules (IPGs), which are considered second messengers of insulin action. In the present work, we document in isolated normal rat adipocytes and hepatocytes that GLP-1 exerts a rapid decrease of the radiolabelled glycosylphosphatidylinositols (GPIs)--precursors of IPGs--in the same manner as insulin, indicating their hydrolysis and the immediate short-lived generation of IPGs. Thus, IPGs could be mediators in the GLP-1 actions in adipose tissue and liver, as well as in skeletal muscle, through GLP-1 receptors which are, at least functionally, different from that of the pancreatic B-cell.
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PMID:Inositolphosphoglycans possibly mediate the effects of glucagon-like peptide-1(7-36)amide on rat liver and adipose tissue. 958 Jan 53

Phosphoenolpyruvate carboxykinase (PEPCK) is a rate-controlling enzyme in hepatic gluconeogenesis, and it therefore plays a central role in glucose homeostasis. The rate of transcription of the PEPCK gene is increased by glucagon (via cAMP) and glucocorticoids and is inhibited by insulin. Under certain circumstances glucose also decreases PEPCK gene expression, but the mechanism of this effect is poorly understood. The glucose-mediated stimulation of a number of glycolytic and lipogenic genes requires the expression of glucokinase (GK) and increased glucose metabolism. HL1C rat hepatoma cells are a stably transfected line of H4IIE rat hepatoma cells that express a PEPCK promoter-chloramphenicol acetyltransferase fusion gene that is regulated in the same manner as the endogenous PEPCK gene. These cells do not express GK and do not normally exhibit a response of either the endogenous PEPCK gene, or of the trans-gene, to glucose. A recombinant adenovirus that directs the expression of glucokinase (AdCMV-GK) was used to increase glucose metabolism in HL1C cells to test whether increased glucose flux is also required for the repression of PEPCK gene expression. In AdCMV-GK-treated cells glucose strongly inhibits hormone-activated transcription of the endogenous PEPCK gene and of the expressed fusion gene. The glucose effect on PEPCK gene promoter activity is blocked by 5 mM mannoheptulose, a specific inhibitor of GK activity. The glucose analog, 2-deoxyglucose mimics the glucose response, but this effect does not require GK expression. 3-O-methylglucose is ineffective. Glucose exerts its effect on the PEPCK gene within 4 h, at physiologic concentrations, and with an EC50 of 6.5 mM, which approximates the Km of glucokinase. The effects of glucose and insulin on PEPCK gene expression are additive, but only at suboptimal concentrations of both agents. The results of these studies demonstrate that, by inhibiting PEPCK gene transcription, glucose participates in a feedback control loop that governs its production from gluconeogenesis.
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PMID:The repression of hormone-activated PEPCK gene expression by glucose is insulin-independent but requires glucose metabolism. 972 36

To evaluate the pattern of plasma cyclic adenosine 3',5'-monophosphate, cyclic guanosine 3',5'-monophosphate, atrial natriuretic factor and glucagon levels in different stages of chronic liver diseases, we measured these variables in 20 normal subjects, 25 patients with genetic hemochromatosis, associated with liver cirrhosis in 19 cases and not in six, eight patients with compensated and 15 with decompensated alcoholic or posthepatitic cirrhosis, and 12 with hepatocellular carcinoma. All variables were within the normal range in non-cirrhotic hemochromatotic patients. Cyclic adenosine 3',5'-monophosphate levels were within the normal range (9.5-15.7 nmol/l) in hemochromatotic cirrhotics and elevated in other patients. Cyclic guanosine 3',5'-monophosphate, atrial natriuretic factor and glucagon were above the normal ranges (1.92-5.91 nmol/l, 8.8-62.7 ng/l, and 39-165 ng/l, respectively) in most patients with cirrhosis both with and without hemochromatosis and in most individuals with hepatocellular carcinoma. Cyclic guanosine 3',5'-monophosphate correlated with atrial natriuretic factor in the former groups but not in the latter. These findings indicate that glucagon and atrial natriuretic factor hypersecretion is an early event in cirrhosis, regardless of its etiology. In hepatocellular carcinoma, the underlying cirrhosis may account for most hormonal and metabolic changes although cyclic guanosine 3',5'-monophosphate increases could also be due to the neoplastic process per se.
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PMID:Pattern of plasma cyclic nucleotides and related hormones in liver cirrhosis and hepatocellular carcinoma. 980 95

Shifting rats to a protein-free, carbohydrate-rich diet, although not starvation, resulted in the appearance of mRNA for, and activity of, 3-phosphoglycerate dehydrogenase (3-PGDH) in liver as well as in a marked decrease in plasma cystine concentration. Refeeding with protein caused a 50% decrease in the mRNA in 8 h and its complete disappearance within 24 h, followed by a slower disappearance of the enzymic activity. Intraperitoneal administration of cysteine or methionine to protein-starved rats decreased the mRNA by 50-60% after 8 h. However, the repeated administration of cysteine failed to cause the complete disappearance of this mRNA in 24 h. In hepatocytes in primary culture, cysteine plus methionine and glucagon had, independently, an approx. 4-fold inhibitory effect on the abundance of the 3-PGDH mRNA and caused its almost complete disappearance when tested together. Insulin had an approx. 2-fold stimulatory effect, which was antagonized by cysteine plus methionine but was still apparent in the presence of glucagon. Nuclear run-on experiments and analysis of the stability of the mRNA with 5,6-dichlorobenzimidazole riboside, an inhibitor of RNA polymerase II, suggested that the effect of cysteine plus methionine was due to destabilization of the mRNA, whereas the effect of glucagon was exerted on transcription. Cysteine, but not methionine, inhibited the accumulation of 3-PGDH mRNA in FTO2B hepatoma cells. In conclusion, the dietary control of the expression of the 3-PGDH gene in liver seems to involve the negative effects of cysteine and glucagon and the positive effect of insulin.
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PMID:Role of cysteine in the dietary control of the expression of 3-phosphoglycerate dehydrogenase in rat liver. 1054 28

A pancreatic carcinoma, associated with elevated serum alpha-fetoprotein level, was resected from a 67-year-old man. The tumor was strongly suggested to be an acinar cell carcinoma of the pancreas, based on the histological findings of the resected specimen. The tumor measured 12 x 10 x 9 cm, and the cut surface was soft, whitish-yellow, focally necrotic, and hemorrhagic. Under a light microscope, the tumor cells were not arranged in a tubular and trabecular pattern, but rather, showed a tendency toward an acinar structure. Immunohistochemically, alpha 1-antitrypsin- and alpha 1-antichymotrypsin-positive reactions were diffusely positive in most of the tumor cells, while staining for chromogranin, neuron-specific enolase, Grimelius, glucagon, insulin, and alpha-fetoprotein was negative in the tumor cells. We report a large acinar cell carcinoma (associated with elevated serum alpha-fetoprotein level), which had been misdiagnosed as hepatocellular carcinoma preoperatively.
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PMID:Large acinar cell carcinoma of the pancreas in a patient with elevated serum AFP level. 1098 18

An important regulatory element (designated FP330-3') of the ALDH2 promoter mediates activation by hepatocyte nuclear factor 4 (HNF4). This activation of promoter constructs containing this element by HNF4 was reduced by nearly half by 8-Br-cAMP in H4IIEC3 cells, an effect that was blocked by inhibitors of protein kinase A (PKA). Cotransfection assays showed that COUP-TF I, ARP-1, or PPARdelta suppressed the ability of HNF4 to activate the reporter. The repression was potentiated by 8-Br-cAMP. Electrophoretic mobility shift assays revealed that treatment of hepatoma cells or cultured rat hepatocytes with 1 mM 8-Br-cAMP or glucagon reduced binding of FP330-3' by HNF4 by half. In vitro phosphorylation of HNF4 by PKA decreased binding to FP330-3'. Fasting reduced the ALDH2 protein level in liver and kidney, two tissues expressing HNF4, but not heart. These data suggest that ALDH2 expression can be suppressed by cAMP, most likely through phosphorylation of HNF4 by PKA, and this may account for the reduction in enzyme protein during fasting.
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PMID:Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4: inhibition by cyclic AMP and COUP transcription factors. 1181 51

Glucagon has previously been reported to increase serum levels of insulin-like growth factor binding protein-1 (IGFBP-1) in humans. The in vitro effect of glucagon and glucagon-like peptide-1 (7-36) amide (GLP-1) was investigated in Hep G2 human hepatoma cells. The expression of IGFBP-1 mRNA was determined by solution hybridization assay and IGFBP-1 secretion was measured by radioimmunoassay. In contrast to forskolin the peptides glucagon and GLP-1 had no effect on IGFBP-1 mRNA at 3, 6 and 24 h incubation or any detectable effect on the apparent half-life of IGFBP-1 mRNA. However, the exposure to glucagon (10 microg/mL, 2.87 microM) and GLP-1 (1 microM) caused a two-fold stimulation in protein levels of IGFBP-1 after 6 h incubation, declining to control levels after 24 h. This transient effect was dose dependent, remained when transcription was inhibited and required protein synthesis. The regulation of IGFBP-1 secretion by glucagon and GLP-1 appeared to be cAMP independent. In conclusion, glucagon and GPL-1 were shown to have a post-transcriptional stimulatory effect on IGFBP-1 release.
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PMID:Glucagon and GLP-1 stimulate IGFBP-1 secretion in Hep G2 cells without effect on IGFBP-1 mRNA. 1212 3

Extrahepatic glucose release was evaluated during the anhepatic phase of liver transplantation in 14 recipients for localized hepatocarcinoma with mild or absent cirrhosis, who received a bolus of [6,6-2H2]glucose and l-[3-13C]alanine or l-[1,2-13C2]glutamine to measure glucose kinetics and to prove whether gluconeogenesis occurred from alanine and glutamine. Twelve were studied again 7 mo thereafter along with seven healthy subjects. At the beginning of the anhepatic phase, plasma glucose was increased and then declined by 15%/h. The right kidney released glucose, with an arteriovenous gradient of -3.7 mg/dl. Arterial and portal glucose concentrations were similar. The glucose clearance was 25% reduced, but glucose uptake was similar to that of the control groups. Glucose production was 9.5 +/- 0.9 micromol.kg-1. min-1, 30% less than in controls. Glucose became enriched with 13C from alanine and especially glutamine, proving the extrahepatic gluconeogenesis. The gluconeogenic precursors alanine, glutamine, lactate, pyruvate, and glycerol, insulin, and the counterregulatory hormones epinephrine, cortisol, growth hormone, and glucagon were increased severalfold. Extrahepatic organs synthesize glucose at a rate similar to that of postabsorptive healthy subjects when hepatic production is absent, and gluconeogenic precursors and counterregulatory hormones are markedly increased. The kidney is the main, but possibly not the unique, source of extrahepatic glucose production.
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PMID:Nonhepatic glucose production in humans. 1282 85


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