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-1 is synthesised in the liver. The metabolic activity of IGF-1 is regulated by 6 IGF-binding proteins (BPs), the most important being IGFBP-3. IGF-1 acts via its own receptor, which resembles that of insulin. 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 antagonistic in their effects on insulin and some aspects of lipid metabolism. This paper reviews present knowledge on the physiological role of IGF-1 and clinical effects of recombinant IGF-1 (somatomedin-1). The biosynthesis of somatomedin-1 in 1986 enabled the initiation of clinical trials. Somatomedin-1 has many potential uses in the clinic. The most important is replacement therapy in primary IGF-1 deficiency, such as Laron syndrome (primary GH resistance or insensitivity) and in patients who have developed antibodies to hGH. In Laron syndrome, which is characterised by dwarfism, somatomedin-1 stimulates growth and increases muscle and bone mass, as well as normalising blood chemistry. In types 1 and 2 (insulin-dependent and non-insulin-dependent) diabetes mellitus, somatomedin-1 increases the sensitivity to insulin and improves glucose utilisation. Experimental studies indicate that IGF-1 has a role in nerve tissue metabolism, 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-operation, AIDS) and haematopoietic disorders. Adverse effects of somatomedin-1 appear 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 applications in the clinic.
Laron
Z
Z
Endocrine and Diabetes Research Unit, Schneider Children's Medical Center of Israel, Sackler School of Medicine, Tel Aviv University, Petah Tikva, Israel.