Abstract
We studied the growth characteristics of the insulin-producing HIT cells. Although successful in many cell lines such as βTC1, growth arrest could not be obtained with HIT cells left for 3 days without serum. Cytofluorometric analysis showed that about 24% of the cells continuously exposed to serum peaked in the S phase. A similar proportion was found for cells cultured for 1 or 2 days in serum-free medium. A treatment with suramin, disrupting the binding of ligands from their receptors, was associated with a rapid and transient increase in c-fos and c-jun gene expression after suramin removal, in the absence of serum. In addition, HIT cells secrete mitogenic factors, different from IGF-I or IGF-II, acting on insulin-secreting βTC1 cells and on BP-A31 fibroblasts. Chromatography of the medium conditioned by the HIT cells on gel filtration gave two major mitogenic fractions, of hydrodynamic characteristics 33 000 and 3000–10 000. The activity was heat stable and bound to heparin. Comparative studies of the self-regulatory HIT cells, with the βTC1 cells requiring external growth factors, should contribute significantly to our understanding of the regulation of β cell growth.
Similar content being viewed by others
References
Angel, P., Hattori, K., Smeal, T. & Karin, M. (1988).Cell,55, 875–885.
Ashcroft, S.J.H., Hammonds, P. & Harrison, D.E. (1986).Diabetologia,29, 727–733.
Auffray, C. & Rougeon, F. (1980).Eur. J. Biochem.,107, 303–314.
Baxter, R.C. & Martin, J.L. (1989).Prog. Growth Factor Res.,1, 49–68.
Binoux, M., Lassarre, C. & Gourmelin, M. (1986).J. Endocrinol. Metab.,63, 1151–1155.
Bleiberg, I., Harvey, A.K., Smale, G. & Grotendorst, G.R. (1985).J. Cell. Physiol.,123, 161–166.
Bravo, R., Zerial, M., Toschi, L., Schurmann, M., Muller, R., Hirai, S.I., Yaniv, M., Almendral, J.M. & Ryseck, R.P. (1988).Cold Spring Harbor Symp. Quant. Biol.,53, 901–905.
Bréant, B., Lavergne, C. & Rosselin, G. (1990).Diabetologia,33, 586–592.
Bréant, B., Lavergne, C., Astesano, A., Ferrand, N., Asfari, M., Boissard, C., Anteunis, A. & Rosselin, G. (1992).Mt. Sinaï J. Med.,59, 175–185.
Buchou, T., Charollais, R.H. & Mester, J. (1989).Exp. Cell Res. 182, 129–143.
Campisi, J., Medrano, E.E., Morreo, G. & Pardee, A.B. (1982).Proc. Natl. Acad. Sci. USA.,79, 436–444.
Chen, J.C., Shao, Z.M., Sheikh, M.S., Hussain, A., Leroith, D., Roberts, C.T. & Fontana, J.A. (1994).J. Cell Physiol.,158, 69–78.
Coffey, R.J., Leof, E.B., Shipley G.D. & Moses, H.L. (1987),J. Cell. Physiol.,132, 143–148.
Curran, T., Peters, G., Van Beveren, C., Teich, N. & Verma, I.M. (1982).J. Virol.,44, 674–682.
Dalla Favera, R., Gelmann, E.P., Martinotti, S., Franchini, G., Papas, T.S., Gallo, R.C. & Wong-Staal, F. (1982).Proc. Natl. Acad. Sci. USA,79, 6497–6501.
Dubrow, R., Riddle, V.G.H. & Pardee, A.B. (1979).Cancer Res.,39, 2718–2726.
Efrat, S., Linde, S., Kofod, H., Spector, D., Delannoy, M., Grant, S., Hanahan, D. & Baekkeskov, S. (1988).Proc. Natl. Acad. Sci. USA,85, 9037–9041.
Gray, H.E., Buchou, T. & Mester, J. (1987).Exp. Cell. Res.,169, 95–104.
Hammonds, P., Schofield, P.N. & Ashcroft, S.J.H. (1987),FEBS Lett.,213, 149–154.
Hellerström, C. & Swenne, I. (1985).The Diabetic Pancreas, Volk, B.W. & Arquilla, R.E. (eds.), Plenum Press New York, pp. 53–79.
Hill, D.J. & Hogg, J. (1991).Modern Concepts of Insulin-Like Growth Factors. EM Spencer (ed.), Elsevier Science Publishing Co., Inc. pp. 235–240.
Hill, R.S. & Boyd III, A.E. (1985).Diabetes,34, 115–120.
Hogg, J., Han, V.K.M., Clemmons, D.R. & Hill, D.J. (1993).J. Endocrinol.,138, 401–412.
Hosang, M. (1985).J. Cell. Biochem.,29, 265–273.
Lau, L.F. & Nathans, D. (1987).Proc. Natl. Acad. Sci. USA,84, 1182–1186.
Le Bouc, Y., Dreyer, D., Jaeger, F., Binoux, M. & Sondermeyer, P. (1986).FEBS Lett.,196, 108–112.
Le Bouc, Y., Noguiez, P., Sondermeijer, P., Dreyer, D., Girard, F. & Binoux, M. (1987).FEBS Lett.,222, 181–185.
Lemishka, I.R., Farmer, S., Racaniello, V.R. & Sharp, P.A. (1981).J. Mol. Biol.,151, 101–121.
Maake, C. & Reinecke, M. (1993).Cell Tissue Res.,273, 249–259.
Maniatis, T., Frisch, E. & Sambrook, J. (1982). (eds.).Molecular Cloning: A Laboratory Manual. Cold Spring Harbour Laboratory Press: Cold Spring Harbour, New York, pp. 387–389.
Petersen, E.D., Billestrup, N. & Nielsen, J.H. (1990).Biomed. Biochim. Acta,49, 1171–1175.
Piette, J., Hirai, S.H. & Yaniv, M. (1988).Proc. Natl. Acad. Sci. USA,85, 3401–3405.
Ryseck, R.P., Hirai, S.I., Yaniv, M. & Bravo, R. (1988).Nature,334, 535–537.
Santerre, R.F., Cook, R.A., Crisel, R.M.D., Sharp, J.D., Schmidt, R.J., Williams D.C. & Wilson, C.P. (1981).Proc. Natl. Acad. Sci. USA,78, 4339–4343.
Shing, Y., Christofori, G., Hanahan, D., Ono, Y., Sasada, R., Igarashi, K. & Folkman, J. (1993).Science,259, 1604–1607.
Thompson, C.B., Challoner, P.B., Neiman, P.E. & Groudine, M. (1985).Nature,314, 363–366.
Treisman, R. (1985).Cell.42, 889–902.
Treisman, R. (1986).Cell,46, 567–574.
Ullrich, A., Shine, J., Chirgwin, J., Pictet, r., Tischer, E., Rutter, W.J. & Goodman, H.M. (1977).Science,196, 1313–1319.
Werner, S., Hofscheneider, P.H., Sturzl, M., Dick, I. & Roth, W.K. (1989).J. Cell. Physiol.,141, 490–502.
Yamashita, S., Tobinaga, T., Ashizawa, Y., Nagayama, Y., Yokota, A., Harakawa, S., Inoue, S., Hirayu, H., Izumi, M. & Nagataki, S. (1988).Endocrinology,123, 1825–1829.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bréant, B., Lieuvin, A., Lavergne, C. et al. HIT cells secrete β-cell mitogenic factors. Endocr 3, 33–38 (1995). https://doi.org/10.1007/BF02917446
Issue Date:
DOI: https://doi.org/10.1007/BF02917446