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)

Rat hepatocytes whose phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) had been labelled for 60 min with 32P were treated with glucagon for 10 min or phenylephrine for 2 min. Glucagon caused a 20% increase in PIP but no change in PIP2 whereas phenylephrine caused a similar increase in PIP but a 15% decrease in PIP2. Addition of both hormones together for 10 min produced a 40% increase in PIP. A crude liver mitochondrial fraction incubated with [32P]Pi and ADP incorporated label into PIP, PIP2 and phosphatidic acid. The PIP2 was shown to be in contaminating plasma membranes and PIP in both lysosomal and plasma-membrane contamination. A minor but definitely mitochondrial phospholipid, more polar than PIP2, was shown to be labelled with 32P both in vitro and in hepatocytes. The rate of 32P incorporation into PIP was faster in mitochondrial/plasma-membrane preparations from rats treated with glucagon or if 3 microM-Ca2+ and Ruthenium Red were present in the incubation buffer. Loss of 32P from membranes labelled in vitro was shown to be accompanied by formation of inositol 1,4,5-trisphosphate (IP3) and inositol 1,4-bisphosphate, and was faster in preparations from glucagon-treated rats or in the presence of 3 microM-Ca2+. It is concluded that glucagon stimulates both PIP2 phosphodiesterase and phosphatidylinositol kinase activities, as does the presence of 3 microM-Ca2+. The resulting formation of IP3 may be responsible for the observed release of intracellular Ca2+ stores. The roles of a guanine nucleotide regulatory protein and phosphorylation in mediating these effects are discussed.
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PMID:Effects of glucagon and Ca2+ on the metabolism of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in isolated rat hepatocytes and plasma membranes. 303 77

Pancreatic islets isolated from juvenile but not aging adult mice, when infected with a retrovirus carrying polyomavirus middle T oncogene, produced cell lines, mPAC, with characteristics both of pancreatic ductal epithelium and neuroendocrine cells of the islets. Following three cycles of single cell cloning, mPAC cells consisted of two subtypes, a null cell, and a double-positive cell that co-expressed cytokeratin, a marker of ductal epithelium, and A2B5, a neuroendocrine ganglioside expressed in developing islet cells. Two islet cell genes, encoding somatostatin and pancreatic polypeptide, were transcribed at low levels in most mPAC clones, whereas the insulin and glucagon genes were not. Upon inoculation of mice, mPAC cells rapidly formed well-differentiated ductal adenocarcinomas that expressed cytokeratin but not the islet cell markers. The mPAC phenotype may result from a specific dedifferentiation of juvenile islet cells or ductal epithelium induced by middle T protein. Alternatively, mPAC cells may arise by transformation of a multipotential progenitor present within or in juxtaposition to juvenile islets. This cell type could therefore represent one of the targets in human cancers of the pancreatic duct. Moreover, signal transduction systems modulated by middle T, including src-related kinases, phosphatidylinositol kinase, and protein phosphatase 2A, may be involved in pancreatic carcinogenesis.
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PMID:Murine pancreatic ductal adenocarcinoma produced by in vitro transduction of polyoma middle T oncogene into the islets of Langerhans. 752 78

This study investigated in a pancreatic alpha-cell line the effects of chronic exposure to palmitate on the insulin and IGF-I receptor (IGF-IR) and intracellular insulin pathways. alpha-TC1-6 cells were cultured in the presence or absence of palmitate (0.5 mmol/liter) up to 48 h. Glucagon secretion, insulin and IGF-IR autophosphorylation, and insulin receptor substrate (IRS)-1, IRS-2, phosphatidylinositol kinase (PI3K) (p85 alpha), and serine-threonine protein kinase (Akt) phosphorylated (active) forms were measured. Erk 44/42 and p38 phosphorylation (P) (MAPK pathway markers) were also measured. Because MAPK can regulate Pax6, a transcription factor that controls glucagon expression, paired box gene 6 (Pax6) and glucagon gene and protein expression were also measured. Basal glucagon secretion was increased and the inhibitory effect of acute insulin exposure reduced in alpha-TC1 cells cultured with palmitate. Insulin-stimulated insulin receptor phosphorylation was greatly reduced by exposure to palmitate. Similar results were observed with IRS-1-P, PI3K (p85 alpha), and Akt-P. In contrast, with IGF-IR and IRS-2-P, the basal levels (i.e. in the absence of insulin stimulation) were higher in cells cultured with palmitate. Similar data were obtained with Erk 44/42-P and p-38-P. Pax6 and glucagon gene and protein expression were higher in cells cultured with palmitate. In these cells cultured, specifics MAPKs inhibitors were able to reduce both Pax6 and glucagon gene and protein expression. These results indicate that alpha-cells exposed to palmitate show insulin resistance of the IRS-1/PI3K/Akt pathway that likely controls glucagon secretion. In contrast, the IRS-2/MAPKs pathway is stimulated, through an activation of the IGF-IR, leading to increased Pax6 and glucagon expression. Our data support the hypothesis that the chronic elevation of fatty acids contribute to alpha-cell dysregulation frequently observed in type 2 diabetes.
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PMID:Palmitate affects insulin receptor phosphorylation and intracellular insulin signal in a pancreatic alpha-cell line. 2057 22