Nature 323, 169 - 171 (11 September 1986); doi:10.1038/323169a0

Growth restoration of insulin-deficient diabetic rats by recombinant human insulin-like growth factor I

Erika Scheiwiller^*, Hans-Peter Guler^*, Jim Merryweather^†, Carl Scandella^†, Walter Maerki^‡, Jürgen Zapf^* & E. Rudolf Froesch^*

^*Metabolic Unit, University Hospital, CH-8091 Zurich, Switzerland
^†Chiron Corporation, Emeryville, California 94608, USA
^‡Ciba-Geigy, 4002 Basel, Switzerland

Insulin-like growth factor I (IGF-I) and insulin stem from a common precursor, are structural homologues, act through similar receptors and elicit insulin-like and growth-promoting effects in vitro and in vivo ^1,2. Serum IGF-I levels are controlled by growth hormone¹, insulin³⁻⁶ and nutrition⁶⁻¹⁰. Insulin-deficient growth-arrested diabetic animals have reduced serum IGF-I levels which are restored towards normal by insulin but not by growth-hormone treatment³⁻⁶. Here we show that normal growth of diabetic rats is restored by infusion of recombinant human (rh)IGF-I without normalization of the blood sugar level and that insulin acts via an increase of IGF-I synthesis on growth of diabetic rats. We describe a new mechanism of endocrine control of growth in which IGF-I is the major stimulator at the cellular level. Growth hormone and insulin act mainly by modulating the hepatic synthesis of IGF-I.

References

1.	Froesch, E. R. & Zapf, J. Diabetologia 28, 485−493 (1985). | PubMed | ISI | ChemPort |
2.	Zapf, J., & Froesch, E. R. Clin. Endocr. Metab. 13/1, 3−30 (1984).
3.	Eigenmann, J. E. et al. Acta endocr. 85, 818−822 (1977). | PubMed | ISI | ChemPort |
4.	Phillips, L. S. & Young, H. S. Diabetes 25, 516−527 (1976). | PubMed | ISI | ChemPort |
5.	Phillips, L. S. & Orawski, A. T. Diabetes 26, 864−869 (1977). | PubMed | ISI | ChemPort |
6.	Miller, L. L., Schalch, D. S. & Draznin, B. Endocrinology 108, 1265−1271 (1981). | PubMed | ISI | ChemPort |
7.	Cree, T. C. & Schalch, D. S. Endocrinologyy 117, 667−673 (1985). | ChemPort |
8.	Schalch, D. S. & Cree, T. C. Endocrinology 117, 2307−2312 (1985). | PubMed | ISI | ChemPort |
9.	Clemmons, D. R. et al. J. clin. Endocr. Metab. 53, 1247−1250 (1981). | PubMed | ISI | ChemPort |
10.	Hintz, R. L., Suskind, R. & Amatayakul, K. J. Pediat. 92, 153−156 (1978). | PubMed | ISI | ChemPort |
11.	Schoenle, E., Zapf, J., Humbel, R.E. & Froesch, E. R. Nature 296, 252−253 (1982). | PubMed | ISI | ChemPort |
12.	Greenspan, F. S., Li, C. H., Simpson, M. E. & Evans, H. M. Endocrinology 45, 455−463 (1949). | ISI | ChemPort |
13.	Schlumpf, U., Heimann, R., Zapf, J. & Froesch, E. R. Acta endocr. 81, 28−42 (1976). | PubMed | ISI | ChemPort |
14.	Schmid, Ch., Steiner, Th. & Froesch, E. R. in Insulin-like Growth Factors/ Somatomedins (ed. Spencer, M.) 13−29 (de Gruyter, New York, 1983).
15.	Schoenle, E., Zapf, J., Hauri, Ch., Steiner, Th. & Froesch, E. R. Acta endocr. 108, 167−174 (1985). | PubMed | ISI | ChemPort |
16.	Zapf, J., Hauri, C., Waldvogel, M. & Froesch, E. R. J. clin. Invest. 77 (in the press).
17.	Schoenle, E., Zapf, J. & Froesch, E. R. Diabetologia 13, 243−249 (1977). | PubMed | ISI | ChemPort |
18.	Poggy, C., Le Marchand-Brustel, Y., Zapf, J., Froesch, E. R. & Freychet, P. Endocrinology 105, 723−730 (1979). | PubMed |
19.	Meuli, C. & Froesch, E. R. Eur. J. din. Invest. 5, 93−99 (1975). | ChemPort |
20.	Schmid, Ch., Steiner, Th. & Froesch, E. R. Calcif. Tissue Int. 35, 578−585 (1983). | PubMed | ISI | ChemPort |
21.	Widmer, U., Schmid, Ch., Zapf, J. & Froesch, E. R. Acta endocr. 108, 237−244 (1985). | PubMed | ISI | ChemPort |
22.	Meuli, C., Zapf, J. & Froesch, E. R. Diabetologia 14, 253−259 (1978).
23.	Zapf, J. et al. J. clin. Invest. 63, 1077−1084 (1979). | PubMed | ISI | ChemPort |
24.	Schwander, J. C., Hauri, C., Zapf, J. & Froesch, E. R. Endocrinology 113, 297−305 (1983). | PubMed | ISI | ChemPort |
25.	Schmid, Ch., Steiner, Th. & Froesch, E. R. FEBS Lett. 173, 48−52 (1984). | Article | PubMed | ISI | ChemPort |
26.	Schmid, Ch., Steiner, Th. & Froesch, E.R. FEBS Lett. 161, 117−121 (1983). | Article | PubMed | ISI | ChemPort |
27.	Kurtz, A., Jelkmann, W. & Bauer, Ch. FEBS Lett. 149, 105−108 (1982). | Article | PubMed | ISI | ChemPort |