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)

A transient rise in cyclic guanosine 3' : 5' monophosphate (c-GMP) in the liver was observed in rats in vivo 10--20 min after partial hepatectomy. A similar increase in c-GMP in the liver was also found in rats in vivo 15 min after infusion of TGH solution (a mixture of triiodothyronine, glucagon, and heparin). In both cases, inductions of ornithine decarboxylase [EC 4.1.1.17] and tyrosine aminotransferase [EC 2.6.1.5] were found 4 hr after the beginning of the experiments. Later, 22 hr after the surgical intervention or hormone infusion, thymidine kinase [EC 2.7.1.21] was activated and liver slices were able to incorporate [3H]thymidine into DNA. These biochemical phenomena were observed commonly in regenerating liver as well as in the liver of rats infused with TGH solution. c-GMP, but not c-AMP, could induce ornithine decarboxylase and tyrosine aminotransferase in isolated, perfused liver.
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PMID:Involvement of cyclic GMP in the initial stage of hepatocytes proliferation. 1 43

Several hormones, including insulin, glucagon, and glucocorticoids, regulate the expression of the rate-limiting gluconeogenic enzyme, phosphoenolpyruvate carboxykinase [GTP: oxaloacetate carboxy-lyase (transphosphorylating); EC 4.1.1.32; PEPCK] in liver. In this report we demonstrate that retinoic acid (RA) also regulates PEPCK expression by inducing a 3-fold increase in the rate of transcription of the PEPCK gene. A RA response element located between -468 and -431 in the PEPCK promoter mediates a 7-fold increase in expression of a chimeric construct containing the basal PEPCK promoter ligated to the chloramphenicol acetyltransferase reporter gene. This element confers RA responsiveness through the heterologous thymidine kinase promoter and functions relatively independent of position and orientation. An 18-base-pair core sequence (-451 to -434) (i) mediates an effect of RA on PEPCK gene expression and contains motifs found in two other RA response elements; (ii) corresponds to AF1, an accessory factor element that is an integral component of the complex glucocorticoid response unit in the PEPCK gene promoter; (iii) is in a region involved in the developmental expression of the PEPCK gene; and (iv) shows homology to elements involved in the tissue-specific regulation of genes, including the hepatic apolipoprotein genes and the alpha 1-antitrypsin gene.
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PMID:A retinoic acid response element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene. 184 96

Pyruvate kinase is a major regulatory enzyme of glycolysis. Transcription of the L-type pyruvate kinase (L-PK) gene in rat liver is induced by feeding a carbohydrate-rich diet. To investigate the regulatory DNA sequences required for this response, primary hepatocytes were transfected with plasmids containing the 5'-flanking sequence of the rat L-PK gene fused to the chloramphenicol acetyltransferase (CAT) gene. Sequences from -4300 to +12 of the L-PK gene directed an increase in CAT activity when hepatocytes were switched from media containing 10 mM lactate to 25 mM glucose. Average induction was 17-fold (n = 13; S.E. = 2.9). Addition of fructose to the media also induced CAT activity. Carbohydrate regulation of the L-PK promoter was retained with 5'-deletions to -197, but constructs deleted to -96 were completely unresponsive. The 101-base pair fragment from -197 to -96 of the L-PK gene can confer carbohydrate regulation when fused in either orientation to the heterologous thymidine kinase promoter, thus defining a carbohydrate response element in this region. Expression of the transfected gene was regulated by insulin and glucagon in a pattern similar to that seen for the endogenous L-PK gene, suggesting that control of L-PK promoter activity was responsible for carbohydrate-mediated changes in L-PK mRNA production.
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PMID:Localization of the carbohydrate response element of the rat L-type pyruvate kinase gene. 202 84

Interactions of nuclear proteins with cis-control elements are involved in the programmed developmental expression of the islet polypeptide hormone genes. Three transcriptional control elements within 300 base pairs of the 5'-flanking region of the rat glucagon gene interact with regulatory cellular proteins and direct transcription only in glucagon-producing islet cells. Two islet cell-specific enhancer-like elements (G2, G3) act together with the glucagon promoter (including the G1 element), which confers A cell specificity of glucagon gene expression. In the present study, the G3 element was analyzed in detail by protein binding and in vivo and in vitro transcription assays. Mutational analyses showed that the sequence of the G3 element comprises two distinct protein-binding domains: a more upstream domain A (5'-CGCCTGA-3'), and a more downstream domain B (5'GATTGAAGGGTGTA-3'). Binding of proteins to these two domains is mutually exclusive. Domain A, but not domain B, is responsible for both functional protein binding and the enhancement of transcription from the glucagon or thymidine kinase gene promoter chloramphenicol acetyltransferase reporter gene transfected in vivo into glucagon-producing islet cells (InR1-G9) and transcribed in vitro in a HeLa cell-free transcription system. In islet cell extracts, the Southwestern blot technique labeled a protein of 45 kDa binding to domain A within G3. We conclude that although the G3 sequence contains two protein-binding motifs, the organization of the G3 enhancer-like element is not bipartite. The islet cell specificity of the G3 element is conferred by a tissue-specific transcription factor or protein complex interacting with domain A of G3. This protein or protein complex recognizes different DNA sequences and provides promoter as well as enhancer activity because it binds also to the apparently unrelated sequence of the G1 promoter element.
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PMID:A pancreatic islet cell-specific enhancer-like element in the glucagon gene contains two domains binding distinct cellular proteins. 216 Apr 64

Thirteen patients who underwent 40% to 80% removal of their livers had blood samples drawn initially and daily on postoperative days 1 to 7. The enzyme marker of heightened polyamine metabolism, ornithine decarboxylase, and the indicator of DNA synthesis, thymidine kinase, were measured. In addition, the hormones (insulin, glucagon, estradiol and androgen), which in animals are known to reflect and possibly modulate regeneration, were measured. Changes in all these indices followed the same pattern as in rats, dogs and swine but at a slower rate. Ornithine decarboxylase and estradiol increased within 24 hr, but thymidine kinase and insulin rises did not become statistically significant until 3 to 5 days. Using these plasma or serum indices as surrogate measures of biochemical events in the liver itself, regeneration reached a maximum after 4 or 5 days. By computed tomography scan analysis, restoration of hepatic cell mass was not complete until 3 wk.
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PMID:Hormonal and enzymatic parameters of hepatic regeneration in patients undergoing major liver resections. 222 10

Although portal blood has been shown to be more hepatotrophic than peripheral venous blood, the origin and nature of the factors responsible remain obscure. In this study the effect of partial ileocolectomy (IC) or partial ileal resection (I) on the regenerative response after 50% partial hepatectomy (PH) in the pig was investigated using thymidine kinase activity and mitotic figures as indices of regeneration. IC with 50% partial hepatectomy resulted in a significantly greater regenerative response on the 3rd day than hepatectomy alone or hepatectomy plus partial I. Levels of plasma insulin were elevated after PH and I but not after IC, although there were no significant differences in levels of plasma glucagon or plasma glucose. Levels of aspartate amino-transferase were similar in all groups. These results extend previous data and suggest that the proximal colon may be the source of a regeneration inhibitory factor.
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PMID:Ileocolectomy enhances the regenerative response after partial hepatectomy in the pig. 233 96

Orthotopic liver transplantation was performed in two groups of dogs; Group I animals consisted of large dogs that served as recipients of livers obtained from smaller dogs while Group II animals consisted of dogs that received liver from donor dogs of nearly the same size. The small-for-size livers transplanted into the Group I dogs rapidly increased in size over the course of 2 weeks until they achieved a size equal to that originally present in the larger recipient dogs. In contrast, the livers transplanted into dogs of the same size as the donors underwent some degree of atrophy. In both groups of animals, plasma levels of insulin and glucagon and hepatic (graft) activities of thymidine kinase and ornithine decarboxylase were followed serially. The only difference between the two groups of animals for these measures was that the ornithine decarboxylase activity rose to a greater degree in the liver that underwent graft enlargement. These data suggest that recipient size determines, at least in part, liver graft size once it is transplanted. These data also suggest that of the parameters followed, only ornithine decarboxylase activity parallels the finding of growth of the transplanted liver.
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PMID:Evidence that host size determines liver size: studies in dogs receiving orthotopic liver transplants. 354 8

In this study, we analyzed the role of the TATA box in the regulation of the phosphoenolpyruvate carboxykinase (PEPCK) gene expression by dexamethasone (DEX), retinoic acid (RA), glucagon (via cAMP) and insulin (INS). The PEPCK TATA box (TATTTAAA) was absolutely required for both basal promoter activity and hormone-mediated transactivation. However, the relative induction of PEPCK gene expression by DEX, RA and cAMP, and its repression by INS, remained unaltered despite the substitution of the PEPCK TATA box with TATA elements from the herpes simplex virus-thymidine kinase gene, gene 33 or a consensus TATA box sequence, TATAAA. The results indicate that the TATA box serves a permissive, but not defining, function in the response of the PEPCK gene to hormones, and that this function can be equally facilitated by heterologous TATA box elements.
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PMID:The role of the TATA box in the hormonal regulation of phosphoenolpyruvate carboxykinase gene expression. 748 24

Tyrosine aminotransferase gene expression is confined to parenchymal cells of the liver, is inducible by glucocorticoids and glucagon, and is repressed by insulin. Three enhancers control this tissue-specific and hormone-dependent activity, one of which, located at -11 kb, is implicated in establishing an active expression domain. We have studied in detail this important regulatory element and have identified a 221-bp fragment containing critical enhancer sequences which stimulated the heterologous thymidine kinase promoter more than 100-fold in hepatoma cells. Within this region, we have characterized two essential liver-specific enhancer domains, one of which was bound by proteins of the hepatocyte nuclear factor 3 (HNF3) family. Analyses with the dedifferentiated hepatoma cell line HTC suggested that HNF3 alpha and/or -gamma, but not HNF3 beta, are involved in activating the tyrosine aminotransferase gene via the -11-kb enhancer. Genomic footprinting and in vitro protein-DNA binding studies documented cell-type-specific binding of ubiquitous factors to the second essential enhancer domain, which by itself stimulated the thymidine kinase promoter preferentially in hepatoma cells. These results will allow further characterization of the role of these enhancer sequences in developmental activation of the tyrosine aminotransferase gene.
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PMID:The distal enhancer implicated in the developmental regulation of the tyrosine aminotransferase gene is bound by liver-specific and ubiquitous factors. 810 32

The four cell types of gut epithelium, enteroendocrine cells, enterocytes, Paneth cells and goblet cells, arise from a common totipotent stem cell located in the mid portion of the intestinal gland. The secretin-producing (S) cell is one of at least ten cell types belonging to the diffuse neuroendocrine system of the gut. We have examined the developmental relationship between secretin cells and other enteroendocrine cell types by conditional ablation of secretin cells in transgenic mice expressing herpes simplex virus 1 thymidine kinase (HSVTK). Ganciclovir-treated mice showed markedly increased numbers of apoptotic cells at the crypt-villus junction. Unexpectedly, ganciclovir treatment induced nearly complete ablation of enteroendocrine cells expressing cholecystokinin and peptide YY/glucagon (L cells) as well as secretin cells, suggesting a close developmental relationship between these three cell types. In addition, ganciclovir reduced the number of enteroendocrine cells producing gastric inhibitory polypeptide, substance-P, somatostatin and serotonin. During recovery from ganciclovir treatment, the enteroendocrine cells repopulated the intestine in normal numbers, suggesting that a common early endocrine progenitor was spared. Expression of BETA2, a basic helix-loop-helix protein essential for differentiation of secretin and cholecystokinin cells was examined in the proximal small intestine. BETA2 expression was seen in all enteroendocrine cells and not seen in nonendocrine cells. These results suggest that most small intestinal endocrine cells are developmentally related and that a close developmental relationship exists between secretin-producing S cells and cholecystokinin-producing and L type enteroendocrine cells. In addition, our work shows the existence of a multipotent endocrine-committed cell type and locates this hybrid multipotent cell type to a region of the intestine populated by relatively immature cells.
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PMID:Targeted ablation of secretin-producing cells in transgenic mice reveals a common differentiation pathway with multiple enteroendocrine cell lineages in the small intestine. 1045 23


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