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Gene Review

Panc1  -  pancreas protein 1

Mus musculus

Synonyms: Pan-1, Pan1
 
 
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Disease relevance of Pan1

 

Psychiatry related information on Pan1

 

High impact information on Pan1

  • OT receptors have also been identified in other tissues, including the kidney, heart, thymus, pancreas, and adipocytes [10].
  • The absence of a major transcript in the pancreas and thyroid (deletions from both families) and an eye-specific transcript (deletion from one family), together with residual expression of some GLIS3 transcripts, seems to explain the incomplete clinical manifestations in these individuals [11].
  • However, what attracts or restricts broadly autoreactive lymphocyte pools to the pancreas remains unclear [12].
  • In this issue of Cell, propose that a defect in a subset of sensory neurons innervating the pancreas plays a major role in initiating the chain of events that will lead to local inflammation, islet destruction, and autoimmune diabetes [13].
  • Delivering the neuropeptide substance P by intra-arterial injection into the NOD pancreas reverses abnormal insulin resistance, insulitis, and diabetes for weeks [12].
 

Chemical compound and disease context of Pan1

  • The effects of starvation and refeeding and of obesity on pancreatic alpha2- and beta-cell responses to glucose or tolbutamide were studied with the isolated rat or mouse pancreas perfused with an amino acid mixture in the presence and absence of glucose [14].
  • These findings suggest that the profound depletion of pancreatic glutathione caused by hyperstimulation of the pancreas with caerulein is critically important in the pathogenesis of acute caerulein-induced pancreatitis [15].
  • Luminal bile salts appear to provide a physiologic protection against necrotizing pancreatitis, at least in part, both by inhibiting the release of CCK and by promoting resistance of the pancreas to CCK excessive stimulation in vivo [16].
  • These studies demonstrate a protective effect of prostaglandin on the pancreas and suggest a role for endogenous prostaglandins in the pathophysiology of pancreatitis [17].
  • We have found that, in normal mice, substance P levels in the pancreas and pancreatic acinar cell expression of NK1R are both increased during secretagogue-induced experimental pancreatitis [18].
 

Biological context of Pan1

  • Given the essential role of IPF1 in pancreas development, it is likely that this autosomal recessive mutation is the cause of the pancreatic agenesis phenotype in this patient [19].
  • The timing of cyst formation indicates that full-length polycystin is required for normal morphogenesis during elongation and maturation of tubular structures in the kidney and pancreas [20].
  • Glut-2 is thus required to maintain normal glucose homeostasis and normal function and development of the endocrine pancreas [21].
  • We show that microinjection of a construct in which the elastase I promoter/enhancer is fused to a gene for diphtheria toxin A polypeptide results in birth of mice lacking a normal pancreas because of expression of the toxin in pancreatic acinar cells [22].
  • Second, in pancreas it promoted proliferation of both acinar cells and fibroblasts and focally altered acinar cell differentiation [23].
 

Anatomical context of Pan1

 

Associations of Pan1 with chemical compounds

  • Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1alpha (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses [27].
  • In streptozocin diabetic mice 300 islets restored normoglycemia; beta cell replication in transplanted islets was similar to replication in normal pancreas and beta cell mass in the graft remained constant [28].
  • In the pancreas from animals starved for 3 d, glucose and tolbutamide suppression of alpha2-cells took place in the absence of demonstrable changes of insulin release [14].
  • Morphometric analysis verified a six-fold increase in beta cell mass/pancreas, a two-fold increase in 5-bromo-2'-deoxyuridine incorporation, a four-fold increase in the number of beta cells per pancreas area, and a two-fold increase in cell size in transgenic compared with wild-type mice at 5 weeks [29].
  • Similarly, PGE2 (0.10 microgram/g body wt) diminished the magnitude of the increase in in-vitro protein discharge and the elevated concentrations of trypsinogen and chymotrypsinogen in pancreas fragments taken from mice given the CDE diet [30].
 

Physical interactions of Pan1

  • Hepatocyte nuclear factors (HNFs) -1alpha, -3beta, -4alpha, and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in beta-cell development and function [31].
  • Given its wide tissue distribution, CFEX also may contribute to transcellular Cl(-) transport in additional epithelia such as the pancreas and contribute to transmembrane Cl(-) transport in nonepithelial tissues such as the heart [32].
  • Immunohistological studies of native and grafted rat pancreas tissue with mouse anti-rat monoclonal antibodies revealed an unexpected staining pattern of MRC Ox 39 which binds specifically to rat interleukin-2 (IL-2) receptors [33].
  • Cytokines have been regarded as effector molecules responsible for beta-cell death and major histocompatibility complex hyperexpression in endocrine pancreas of type I diabetes [34].
  • No saturable gastrin binding to normal nontransgenic mouse pancreas was found [35].
 

Enzymatic interactions of Pan1

 

Regulatory relationships of Pan1

 

Other interactions of Pan1

  • Thus, Hlxb9 is key to normal pancreas development and function [24].
  • We now show that mice homozygous for a targeted mutation in the Ipf1 gene selectively lack a pancreas [42].
  • Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas [43].
  • The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas [37].
  • Here, to test this idea, we analysed pancreas development in mice genetically altered at several steps in the Notch signalling pathway [44].
 

Analytical, diagnostic and therapeutic context of Pan1

  • Localization of antibody binding in pancreas was similar to that of liver, while in heart ventricle the immunofluorescence pattern was consistent with binding to the intercalated disc [26].
  • Inoculation of mouse, monkey and human cell cultures with homogenates from the patient's pancreas led to isolation of a virus [4].
  • When the cloned rat elastase I gene with 7 kb upstream and 5 kb downstream flanking sequences was introduced into mice by microinjection into fertilized eggs, the gene was expressed in a pancreas-specific manner [45].
  • Genes encoding homeodomain-containing proteins potentially involved in endocrine pancreas development were isolated by combined in silico and nested-PCR approaches [46].
  • Similar transformations occur in organ cultures employing wild-type pancreatic endoderm and spleen mesenchyme, revealing the developmental plasticity of the pancreas and that precise spatial and temporal control of tissue interactions are required for development of both organs [47].

References

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  2. TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Jhappan, C., Stahle, C., Harkins, R.N., Fausto, N., Smith, G.H., Merlino, G.T. Cell (1990) [Pubmed]
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  5. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nestle, F.O., Alijagic, S., Gilliet, M., Sun, Y., Grabbe, S., Dummer, R., Burg, G., Schadendorf, D. Nat. Med. (1998) [Pubmed]
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  10. The oxytocin receptor system: structure, function, and regulation. Gimpl, G., Fahrenholz, F. Physiol. Rev. (2001) [Pubmed]
  11. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Senée, V., Chelala, C., Duchatelet, S., Feng, D., Blanc, H., Cossec, J.C., Charon, C., Nicolino, M., Boileau, P., Cavener, D.R., Bougnères, P., Taha, D., Julier, C. Nat. Genet. (2006) [Pubmed]
  12. TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes. Razavi, R., Chan, Y., Afifiyan, F.N., Liu, X.J., Wan, X., Yantha, J., Tsui, H., Tang, L., Tsai, S., Santamaria, P., Driver, J.P., Serreze, D., Salter, M.W., Dosch, H.M. Cell (2006) [Pubmed]
  13. Sensory neurons link the nervous system and autoimmune diabetes. Bour-Jordan, H., Bluestone, J.A. Cell (2006) [Pubmed]
  14. Adaptations of alpha2- and beta-cells of rat and mouse pancreatic islets to starvation, to refeeding after starvation, and to obesity. Matschinsky, F.M., Rujanavech, C., Pagliara, A., Norfleet, W.T. J. Clin. Invest. (1980) [Pubmed]
  15. Glutathione monoethyl ester ameliorates caerulein-induced pancreatitis in the mouse. Neuschwander-Tetri, B.A., Ferrell, L.D., Sukhabote, R.J., Grendell, J.H. J. Clin. Invest. (1992) [Pubmed]
  16. Protective action of luminal bile salts in necrotizing acute pancreatitis in mice. Gomez, G., Townsend, C.M., Green, D.W., Rajaraman, S., Uchida, T., Greeley, G.H., Soloway, R.D., Thompson, J.C. J. Clin. Invest. (1990) [Pubmed]
  17. Effects of prostaglandin and indomethacin on diet-induced acute pancreatitis in mice. Coelle, E.F., Adham, N., Elashoff, J., Lewin, K., Taylor, I.L. Gastroenterology (1983) [Pubmed]
  18. Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury. Bhatia, M., Saluja, A.K., Hofbauer, B., Frossard, J.L., Lee, H.S., Castagliuolo, I., Wang, C.C., Gerard, N., Pothoulakis, C., Steer, M.L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  19. Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Stoffers, D.A., Zinkin, N.T., Stanojevic, V., Clarke, W.L., Habener, J.F. Nat. Genet. (1997) [Pubmed]
  20. Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Lu, W., Peissel, B., Babakhanlou, H., Pavlova, A., Geng, L., Fan, X., Larson, C., Brent, G., Zhou, J. Nat. Genet. (1997) [Pubmed]
  21. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Guillam, M.T., Hümmler, E., Schaerer, E., Yeh, J.I., Birnbaum, M.J., Beermann, F., Schmidt, A., Dériaz, N., Thorens, B., Wu, J.Y. Nat. Genet. (1997) [Pubmed]
  22. Cell lineage ablation in transgenic mice by cell-specific expression of a toxin gene. Palmiter, R.D., Behringer, R.R., Quaife, C.J., Maxwell, F., Maxwell, I.H., Brinster, R.L. Cell (1987) [Pubmed]
  23. Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Sandgren, E.P., Luetteke, N.C., Palmiter, R.D., Brinster, R.L., Lee, D.C. Cell (1990) [Pubmed]
  24. Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice. Harrison, K.A., Thaler, J., Pfaff, S.L., Gu, H., Kehrl, J.H. Nat. Genet. (1999) [Pubmed]
  25. Tissue-specific expression of mouse-alpha-amylase genes: nucleotide sequence of isoenzyme mRNAs from pancreas and salivary gland. Hagenbüchle, O., Bovey, R., Young, R.A. Cell (1980) [Pubmed]
  26. A protein homologous to the 27,000 dalton liver gap junction protein is present in a wide variety of species and tissues. Hertzberg, E.L., Skibbens, R.V. Cell (1984) [Pubmed]
  27. Defective insulin secretion in hepatocyte nuclear factor 1alpha-deficient mice. Pontoglio, M., Sreenan, S., Roe, M., Pugh, W., Ostrega, D., Doyen, A., Pick, A.J., Baldwin, A., Velho, G., Froguel, P., Levisetti, M., Bonner-Weir, S., Bell, G.I., Yaniv, M., Polonsky, K.S. J. Clin. Invest. (1998) [Pubmed]
  28. Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice. Montaña, E., Bonner-Weir, S., Weir, G.C. J. Clin. Invest. (1993) [Pubmed]
  29. Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia. Bernal-Mizrachi, E., Wen, W., Stahlhut, S., Welling, C.M., Permutt, M.A. J. Clin. Invest. (2001) [Pubmed]
  30. Protective effects of PGE2 on diet-induced acute pancreatitis in mice. Manabe, T., Steer, M.L. Gastroenterology (1980) [Pubmed]
  31. Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta. Shih, D.Q., Heimesaat, M., Kuwajima, S., Stein, R., Wright, C.V., Stoffel, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  32. Identification of a chloride-formate exchanger expressed on the brush border membrane of renal proximal tubule cells. Knauf, F., Yang, C.L., Thomson, R.B., Mentone, S.A., Giebisch, G., Aronson, P.S. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  33. Staining of native and grafted exocrine rat pancreas by an interleukin-2 receptor specific monoclonal antibody. Knoop, M., McMahon, R.F., Hutchinson, I.V. Acta Histochem. (1990) [Pubmed]
  34. Pancreatic beta-cell-selective production of tumor necrosis factor-alpha induced by interleukin-1. Yamada, K., Takane, N., Otabe, S., Inada, C., Inoue, M., Nonaka, K. Diabetes (1993) [Pubmed]
  35. Novel expression of gastrin (CCK-B) receptors in pancreatic carcinomas and dysplastic pancreas from transgenic mice. Povoski, S.P., Zhou, W., Longnecker, D.S., Bell, R.H. Am. J. Surg. (1994) [Pubmed]
  36. Structure of the hepatocyte nuclear factor 6alpha and its interaction with DNA. Sheng, W., Yan, H., Rausa, F.M., Costa, R.H., Liao, X. J. Biol. Chem. (2004) [Pubmed]
  37. The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreas. Sosa-Pineda, B., Chowdhury, K., Torres, M., Oliver, G., Gruss, P. Nature (1997) [Pubmed]
  38. Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas. Vinter-Jensen, L., Juhl, C.O., Teglbjaerg, P.S., Poulsen, S.S., Dajani, E.Z., Nexø, E. Gastroenterology (1997) [Pubmed]
  39. IA1 is NGN3-dependent and essential for differentiation of the endocrine pancreas. Mellitzer, G., Bonné, S., Luco, R.F., Van De Casteele, M., Lenne-Samuel, N., Collombat, P., Mansouri, A., Lee, J., Lan, M., Pipeleers, D., Nielsen, F.C., Ferrer, J., Gradwohl, G., Heimberg, H. EMBO J. (2006) [Pubmed]
  40. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Yoshitomi, H., Zaret, K.S. Development (2004) [Pubmed]
  41. GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas development. Harmon, E.B., Apelqvist, A.A., Smart, N.G., Gu, X., Osborne, D.H., Kim, S.K. Development (2004) [Pubmed]
  42. Insulin-promoter-factor 1 is required for pancreas development in mice. Jonsson, J., Carlsson, L., Edlund, T., Edlund, H. Nature (1994) [Pubmed]
  43. Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. St-Onge, L., Sosa-Pineda, B., Chowdhury, K., Mansouri, A., Gruss, P. Nature (1997) [Pubmed]
  44. Notch signalling controls pancreatic cell differentiation. Apelqvist, A., Li, H., Sommer, L., Beatus, P., Anderson, D.J., Honjo, T., Hrabe de Angelis, M., Lendahl, U., Edlund, H. Nature (1999) [Pubmed]
  45. Tissue-specific expression of the rat pancreatic elastase I gene in transgenic mice. Swift, G.H., Hammer, R.E., MacDonald, R.J., Brinster, R.L. Cell (1984) [Pubmed]
  46. Opposing actions of Arx and Pax4 in endocrine pancreas development. Collombat, P., Mansouri, A., Hecksher-Sorensen, J., Serup, P., Krull, J., Gradwohl, G., Gruss, P. Genes Dev. (2003) [Pubmed]
  47. Spleen versus pancreas: strict control of organ interrelationship revealed by analyses of Bapx1-/- mice. Asayesh, A., Sharpe, J., Watson, R.P., Hecksher-Sørensen, J., Hastie, N.D., Hill, R.E., Ahlgren, U. Genes Dev. (2006) [Pubmed]
 
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