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Gene Review

ISL1  -  ISL LIM homeobox 1

Homo sapiens

Synonyms: ISLET1, Insulin gene enhancer protein ISL-1, Isl-1, Islet-1
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Disease relevance of ISL1

  • To evaluate this gene in non-insulin-dependent diabetes mellitus (NIDDM), a full-length human Isl-1 cDNA was isolated and the genomic structure was characterized [1].
  • Since Islet-1 is normally expressed before Hu in DRG cells, it is possible that the reduced growth rate of the DRG2 ganglion may partially result from the inability of precociously differentiating Islet-1(+) neurons to further mature, as reflected by Hu antigen expression [2].
  • First-degree relatives of patients with type I diabetes mellitus. Islet-cell antibodies and abnormal insulin secretion [3].
  • Letter: Islet-cell hyperplasia and sudden infant death [4].
  • A weak indication for linkage was obtained between the Isl-1 locus and obesity status defined by a z score over one SD of BMI (n = 226 sib pairs, pi = 0.54 +/- 0.02, P = 0.03) [5].

High impact information on ISL1

  • Motor neurons are not generated without ISL1, although many other aspects of cell differentiation in the neural tube occur normally [6].
  • Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells [7].
  • These results indicate that ISL1, by virtue of its requirement for the formation of dorsal mesenchyme, is necessary for the development of the dorsal exocrine pancreas, and also that ISL1 function in pancreatic endodermal cells is required for the generation of all endocrine islet cells [7].
  • ISL1 is also expressed in mesenchymal cells that surround the dorsal but not ventral evagination of the gut endoderm, which together comprise the pancreatic anlagen [7].
  • We identified a similar Isl1 binding site in the Nkx2-5 AHF enhancer, which in transgenic mouse embryos was essential for activity in a large part of the heart, including the outflow tract [8].

Chemical compound and disease context of ISL1


Biological context of ISL1


Anatomical context of ISL1


Associations of ISL1 with chemical compounds


Physical interactions of ISL1

  • ISL1 physically interacts with BETA2 to promote insulin gene transcriptional synergy in non-beta cells [13].

Regulatory relationships of ISL1

  • Islet-1 is expressed in a higher proportion of cells in DRG2 than DRG5, suggesting that cells in DRG2 differentiate more rapidly into neurons than in normal DRG [2].

Other interactions of ISL1

  • The transcription factor PAX4 is located at 7q32 and participates downstream of ISL1 in the transcription factor cascade critical to beta-cell development [12].
  • Using the luciferase assay, we demonstrated that ISL1 and BETA2 could activate insulin gene transcription synergistically [13].
  • The LIM/homeodomain protein islet-1 modulates estrogen receptor functions [17].
  • We find that expression of npn2 is downregulated in isl1-cre;smo mutants, suggesting an isl1/Shh/npn pathway required to affect morphogenesis at the anterior pole of the heart [19].
  • BACKGROUND: Islet transplantation can reduce or eliminate the need for insulin in patients with type 1 diabetes [22].

Analytical, diagnostic and therapeutic context of ISL1


  1. Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM. Riggs, A.C., Tanizawa, Y., Aoki, M., Wasson, J., Ferrer, J., Rabin, D.U., Vaxillaire, M., Froguel, P., Permutt, M.A. Diabetes (1995) [Pubmed]
  2. Differences in neuronal differentiation between the transient cranial (Frorieps') and normal dorsal root ganglia. Avivi, C., Cui, S., Goren, S., Goldstein, R.S. Brain Res. Dev. Brain Res. (2002) [Pubmed]
  3. First-degree relatives of patients with type I diabetes mellitus. Islet-cell antibodies and abnormal insulin secretion. Srikanta, S., Ganda, O.P., Rabizadeh, A., Soeldner, J.S., Eisenbarth, G.S. N. Engl. J. Med. (1985) [Pubmed]
  4. Letter: Islet-cell hyperplasia and sudden infant death. Polak, J.M., Wigglesworth, J.S. Lancet (1976) [Pubmed]
  5. A sib-pair analysis study of 15 candidate genes in French families with morbid obesity: indication for linkage with islet 1 locus on chromosome 5q. Clément, K., Dina, C., Basdevant, A., Chastang, N., Pelloux, V., Lahlou, N., Berlan, M., Langin, D., Guy-Grand, B., Froguel, P. Diabetes (1999) [Pubmed]
  6. Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation. Pfaff, S.L., Mendelsohn, M., Stewart, C.L., Edlund, T., Jessell, T.M. Cell (1996) [Pubmed]
  7. Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Ahlgren, U., Pfaff, S.L., Jessell, T.M., Edlund, T., Edlund, H. Nature (1997) [Pubmed]
  8. Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development. Takeuchi, J.K., Mileikovskaia, M., Koshiba-Takeuchi, K., Heidt, A.B., Mori, A.D., Arruda, E.P., Gertsenstein, M., Georges, R., Davidson, L., Mo, R., Hui, C.C., Henkelman, R.M., Nemer, M., Black, B.L., Nagy, A., Bruneau, B.G. Development (2005) [Pubmed]
  9. Re: "Islet Hyperplasia in Adults: Challenge to Preoperatively Diagnose Non-insulinoma Pancreatogenic Hypoglycemia Syndrome". Pradeep, P.V., Mishra, A., Mishra, S.K. World journal of surgery (2007) [Pubmed]
  10. Differential expression of Islet-1 in neural crest-derived ganglia: Islet-1 + dorsal root ganglion cells are post-mitotic and Islet-1 + sympathetic ganglion cells are still cycling. Avivi, C., Goldstein, R.S. Brain Res. Dev. Brain Res. (1999) [Pubmed]
  11. An overview of the current status of islet cell transplantation as a treatment for diabetes mellitus. Islet cell transplantation, artificial pancreas, or genetic insulin synthesis offer possibilities for physiologic glucose regulation. Kakvan, M., Garber, A.J. Rhode Island medical journal. (1979) [Pubmed]
  12. Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families. Holm, P., Rydlander, B., Luthman, H., Kockum, I. Diabetes (2004) [Pubmed]
  13. ISL1 physically interacts with BETA2 to promote insulin gene transcriptional synergy in non-beta cells. Peng, S.Y., Wang, W.P., Meng, J., Li, T., Zhang, H., Li, Y.M., Chen, P., Ma, K.T., Zhou, C.Y. Biochim. Biophys. Acta (2005) [Pubmed]
  14. Hepatocyte Nuclear Factor 4 Alpha Ligand Binding and F Domains Mediate Interaction and Transcriptional Synergy with the Pancreatic Islet LIM HD Transcription Factor Isl1. Eeckhoute, J., Briche, I., Kurowska, M., Formstecher, P., Laine, B. J. Mol. Biol. (2006) [Pubmed]
  15. A distal enhancer and an ultraconserved exon are derived from a novel retroposon. Bejerano, G., Lowe, C.B., Ahituv, N., King, B., Siepel, A., Salama, S.R., Rubin, E.M., Kent, W.J., Haussler, D. Nature (2006) [Pubmed]
  16. Developmental regulation of the orphan receptor COUP-TF II gene in spinal motor neurons. Lutz, B., Kuratani, S., Cooney, A.J., Wawersik, S., Tsai, S.Y., Eichele, G., Tsai, M.J. Development (1994) [Pubmed]
  17. The LIM/homeodomain protein islet-1 modulates estrogen receptor functions. Gay, F., Anglade, I., Gong, Z., Salbert, G. Mol. Endocrinol. (2000) [Pubmed]
  18. Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Eberhardt, M., Salmon, P., von Mach, M.A., Hengstler, J.G., Brulport, M., Linscheid, P., Seboek, D., Oberholzer, J., Barbero, A., Martin, I., Müller, B., Trono, D., Zulewski, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  19. Isl1 is upstream of sonic hedgehog in a pathway required for cardiac morphogenesis. Lin, L., Bu, L., Cai, C.L., Zhang, X., Evans, S. Dev. Biol. (2006) [Pubmed]
  20. Islet Neogenesis Associated Protein (INGAP) modulates gene expression in cultured neonatal rat islets. Barbosa, H., Bordin, S., Stoppiglia, L., Silva, K., Borelli, M., Del Zotto, H., Gagliardino, J., Boschero, A. Regul. Pept. (2006) [Pubmed]
  21. Enhanced isolated pancreatic islet recovery and functionality in rats by 17beta-estradiol treatment of brain death donors. Eckhoff, D.E., Eckstein, C., Smyth, C.A., Vilatoba, M., Bilbao, G., Rahemtulla, F.G., Young, C.J., Anthony Thompson, J., Chaudry, I.H., Contreras, J.L. Surgery (2004) [Pubmed]
  22. Effect of exenatide on beta cell function after islet transplantation in type 1 diabetes. Ghofaili, K.A., Fung, M., Ao, Z., Meloche, M., Shapiro, R.J., Warnock, G.L., Elahi, D., Meneilly, G.S., Thompson, D.M. Transplantation (2007) [Pubmed]
  23. Diabetes. Islet cell transplantation. Shapiro, A.M., Ryan, E.A., Lakey, J.R. Lancet (2001) [Pubmed]
  24. Characterization of Donor Dendritic Cells and Enhancement of Dendritic Cell Efflux With cc-Chemokine Ligand 21: A Novel Strategy to Prolong Islet Allograft Survival. Fiorina, P., Jurewicz, M., Tanaka, K., Behazin, N., Augello, A., Vergani, A., Von Adrian, U., Smith, N.R., Sayegh, M.H., Abdi, R. Diabetes (2007) [Pubmed]
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