Somatomedin-1 (recombinant insulin-like growth factor-1) - Clinical pharmacology and potential treatment of endocrine and metabolic disorders

Insulin-like growth factor (IGF-1) is a polypeptide of 70 amino acids. The circulatory form of IGF-I is synthesised in the liver. The metabolic activi ty of IGF-1 is regulated by 6 IGF-binding proteins (BPs), the most importan t being IGFBP-3, IGF-1 acts via its own receptor, which resembles that of i nsulin, It has been demonstrated that the effects of growth hormone (GH) on protein metabolism, including growth and the effect on nerve tissue versus trophic effects, are mediated by IGF-1, whereas these 2 hormones are antag onistic in their effects on insulin and some aspects of lipid metabolism Th is paper reviews present knowledge on the physiological role of IGF-I and c linical effects of recombinant IGF-1 (somatomedin-1). The biosynthesis of somatomedin-l in 1986 enabled the initiation of clinica l trials. Somatomedin-l has many potential uses in the clinic. The most imp ortant is replacement therapy in primary IGF-I deficiency, such as Laron sy ndrome (primary GH resistance or insensitivity) and in patients who have de veloped antibodies to hGH. In Laron syndrome, which is characterised by dwa rfism, somatomedin-1 stimulates growth and increases muscle and bone mass, as well as normalising blood chemistry. In types I and 2 (insulin-dependent and non-independent) diabetes mellitus, somatomedin-l increases the sensit ivity to insulin and improves glucose utilisation. Experimental studies indicate that IGF-I has a role in nerve tissue metabol ism, and in humans may contribute to healing of injured nerve tissue. Other current clinical trials using the anabolic properties of somatomedin-1 are studying its effect on osteoporosis, catabolic states (burns, post-operati on. AIDS) and haematopoietic disorders. Adverse effects of somatomedin-1 ap pear to be related to overdosage. In conclusion, somatomedin-1 is an important hormone which has a promising role as replacement therapy and appears to have many other potential applic ations in the clinic.