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Gene Review

Igfals  -  insulin-like growth factor binding protein...

Rattus norvegicus

Synonyms: ALS, Als, Insulin-like growth factor-binding protein complex acid labile subunit
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Disease relevance of Igfals


High impact information on Igfals

  • Stem cells step closer to the clinic: paralysis partially reversed in rats with ALS-like disease [5].
  • Recent studies suggest that the inducible isoform of cyclooxygenase, COX-2, promotes motor neuron loss in rodent models of ALS [6].
  • Combination immunosuppression therapy with long-acting glucocorticoids, cyclosporin-A, and antiserum to rat lymphocytes (ALS) reduced the severity of spontaneous diabetes among BioBreeding/Worcester rats and decreased the frequency of diabetes in susceptible littermates [2].
  • The administration of a short course of ALS (1 ml I.P. days-1, 1, 3 and 5) to the remaining 6 animals greatly prolonged graft survival with all animals remaining normoglycaemic for at lest 4 weeks [7].
  • Malnutrition suppresses ALS and IGF-I expression in a development-dependent manner [8].

Chemical compound and disease context of Igfals

  • Walker 256, Neuroblastoma, and Sarcoma dual-tumor models were used to evaluate the effect of ALS aspiration on the uptake of 3F8 monoclonal antibody, and doxorubicin [9].

Biological context of Igfals


Anatomical context of Igfals

  • We investigated the effects of PGE2, a principal downstream prostaglandin product of COX-2 activity, on motor neuron survival in an organotypic culture model of ALS [6].
  • Circulating acid-labile subunit (ALS) is mainly hepatocyte derived and is GH dependent [12].
  • Similarly, unresponsive WF recipients of BN grafts accepted second Lewis grafts after IT injection of Lewis T cells combined with ALS, 30 or 100 days after primary BN grafts [13].
  • Failure to demonstrate a synergistic effect between enhancing serum and ALS in recipients of pancreatic islet allografts [14].
  • Northern analysis of ALS messenger RNA (mRNA) from adult rat brain, heart, lung, muscle, spleen, testis or ovary, kidney, and liver showed a liver-specific predominant 2-kilobase transcript [15].

Associations of Igfals with chemical compounds

  • A short course of procarbazine hydrochloride (PCH; 50 mg/kg) and antilymphocyte serum (ALS; 5 ml/kg), administered to Lewis (LEW;RT1(1] rats in the first week following transplantation of Brown Norway (BN;RT1n) kidneys, substantially prolonged allograft survival and induced long-term survival in 62% of the grafts [16].
  • Streptozotocin-diabetic rats, untreated or treated with human GH for 5 days, had significantly decreased serum ALS levels and liver ALS mRNA abundance [15].
  • Dexamethasone, an inhibitor of ALS synthesis by hepatocytes, significantly reduced both serum ALS and hepatic ALS mRNA [15].
  • In the present study, the regulatory effects of the cAMP analogs dibutyryl-cAMP (db-cAMP) and 8-bromo-cAMP (8-br-cAMP) on IGF-I, ALS, and IGFBP expression were evaluated in primary cultures of rat hepatocytes, KC as well as in cocultures of hepatocytes and KC [17].
  • The proposed excitotoxic mechanism of ALS, therefore, is most likely mediated through non-NMDA glutamate receptors [18].

Other interactions of Igfals

  • The GH-dependent, hepatocyte-derived acid-labile subunit (ALS) regulates IGF release from the serum by forming ternary complexes containing IGF binding protein (IGFBP)-3 or IGFBP-5 [8].
  • Neither regulation of hepatic GH receptor nor ALS clearance rates could explain the age-dependent effect [8].

Analytical, diagnostic and therapeutic context of Igfals

  • Purification involved ion-exchange chromatography, and affinity chromatography on an IGF-I-IGFBP-3 column, yielding almost 1 mg ALS from 100 ml serum [10].
  • Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS [19].
  • By contrast, treatment with i.t. donor splenocytes plus ALS 2 weeks prior to transplantation prolonged graft survival (100% long-term; mean 90.0 +/- 0.0 days, P < 0.04), and markedly inhibited graft arteriosclerosis (score 0.80 +/- 0.14, P < 0.05; 27 +/- 4% diseased, P < 0.05) [20].
  • Both intravenous and intraperitoneal injection of ALS effectively prevent GVHD in this model [21].
  • Recipient F344 rats were treated with donor (Lewis) splenocytes by intrathymic injection (i.t.) alone (10 x 10(6) cells/lobe); with donor splenocytes i.t. plus a one-time dose of ALS (1 mg) by intraperitoneal injection (i.p.); or with ALS i.p. (1 mg) alone 2 and 6 weeks prior to heterotopic Lewis heart transplantation [20].


  1. Regulation of the acid-labile subunit in sustained endotoxemia. Kong, S.E., Firth, S.M., Baxter, R.C., Delhanty, P.J. Am. J. Physiol. Endocrinol. Metab. (2002) [Pubmed]
  2. Spontaneous diabetes mellitus in the BB/W rat. Effects of glucocorticoids, cyclosporin-A, and antiserum to rat lymphocytes. Like, A.A., Anthony, M., Guberski, D.L., Rossini, A.A. Diabetes (1983) [Pubmed]
  3. A comparative analysis of allelic imbalance events in chemically induced rat mammary, colon, and bladder tumors. Haag, J.D., Brasic, G.M., Shepel, L.A., Newton, M.A., Grubbs, C.J., Lubet, R.A., Kelloff, G.J., Gould, M.N. Mol. Carcinog. (1999) [Pubmed]
  4. The high-affinity glutamate transporters GLT1, GLAST, and EAAT4 are regulated via different signalling mechanisms. Gegelashvili, G., Dehnes, Y., Danbolt, N.C., Schousboe, A. Neurochem. Int. (2000) [Pubmed]
  5. Stem cells step closer to the clinic: paralysis partially reversed in rats with ALS-like disease. Vastag, B. JAMA (2001) [Pubmed]
  6. PGE2 receptors rescue motor neurons in a model of amyotrophic lateral sclerosis. Bilak, M., Wu, L., Wang, Q., Haughey, N., Conant, K., St Hillaire, C., Andreasson, K. Ann. Neurol. (2004) [Pubmed]
  7. Successful intra-splenic transplantation of syngeneic and allogeneic isolated pancreatic islets. Finch, D.R., Wise, P.H., Morris, P.J. Diabetologia (1977) [Pubmed]
  8. Age-dependent regulation of the acid-labile subunit in response to fasting-refeeding in rats. Kong, S.E., Baxter, R.C., Delhanty, P.J. Endocrinology (2002) [Pubmed]
  9. Enhancing the uptake of chemotherapeutic drugs into tumors using an "artificial lymphatic system". DiResta, G.R., Lee, J., Healey, J.H., Larson, S.M., Arbit, E. Annals of biomedical engineering. (2000) [Pubmed]
  10. Purification and characterization of the acid-labile subunit of rat serum insulin-like growth factor binding protein complex. Baxter, R.C., Dai, J. Endocrinology (1994) [Pubmed]
  11. Cloning and characterization of the rat gene for the acid-labile subunit of the insulin-like growth factor binding protein complex. Delhanty, P.J., Baxter, R.C. J. Mol. Endocrinol. (1997) [Pubmed]
  12. The regulation of acid-labile subunit gene expression and secretion by cyclic adenosine 3',5'-monophosphate. Delhanty, P.J., Baxter, R.C. Endocrinology (1998) [Pubmed]
  13. Tolerance induction to cardiac allografts by simultaneous or sequential intrathymic inoculation of disparate alloantigens. Shimomura, K., Hardy, M.A., Oluwole, S.F. Transplantation (1995) [Pubmed]
  14. Failure to demonstrate a synergistic effect between enhancing serum and ALS in recipients of pancreatic islet allografts. Finch, D.R., Morris, P.J. Transplantation (1977) [Pubmed]
  15. Regulation in vivo of the acid-labile subunit of the rat serum insulin-like growth factor-binding protein complex. Dai, J., Baxter, R.C. Endocrinology (1994) [Pubmed]
  16. Specific unresponsiveness to fully allogeneic kidney allografts in rats induced by procarbazine hydrochloride and antilymphocyte serum. Al Mahdi, N., Hutchinson, I.V., Brent, L. Transplantation (1983) [Pubmed]
  17. Regulation of the components of the 150 kDa IGF binding protein complex in cocultures of rat hepatocytes and Kupffer cells by 3',5'-cyclic adenosine monophosphate. Scharf, J.G., Braulke, T., Hartmann, H., Ramadori, G. J. Cell. Physiol. (2001) [Pubmed]
  18. Selective vulnerability of spinal cord motor neurons to non-NMDA toxicity. Saroff, D., Delfs, J., Kuznetsov, D., Geula, C. Neuroreport (2000) [Pubmed]
  19. Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS. Lacy, P.E., Davie, J.M., Finke, E.H. Science (1979) [Pubmed]
  20. Intrathymic tolerance in the Lewis-to-F344 chronic cardiac allograft rejection model. Shin, Y.T., Adams, D.H., Wyner, L.R., Akalin, E., Sayegh, M.H., Karnovsky, M.J. Transplantation (1995) [Pubmed]
  21. Prevention of graft-versus-host disease following small bowel transplantation with polyclonal and monoclonal antilymphocyte serum. The effect of timing and route of administration. Shaffer, D., Ubhi, C.S., Simpson, M.A., Gottschalk, R., Milford, E.L., Maki, T., Monaco, A.P. Transplantation (1991) [Pubmed]
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