Insulin receptor and IGF-I receptor Bioactivity in Health and Disease

Insulin was discovered in 1921 by Banting and Best and its structure elucidated in 1955. The first insulin bioassays appeared in the 1940s. First, rats were injected with a range of known concentrations of purified commercial or ‘standard’ insulin and the subsequent fall in blood glucose levels was measured. Then an unknown sample of human plasma was administered to a rat and its insulin concentration was assumed to be identical to the standard dilution that caused the same fall in glucose levels. Due to poor correlations between measured blood glucose levels and calculated insulin levels, these bioassays were replaced by in vitro bioassays. Metabolic parameters, such as rate of glucose uptake in response to dose-response curves of known insulin concentrations were measured using isolated tissues, such as the hemidiaphragm or epididymal fat pad from the rat. Also these in vitro bioassays for plasma insulin were not very successful due to high inter-assay variability, their laborious nature and due to a growing doubt that they were not specific for insulin. Maybe even more importantly, in 1959 Leonards described a substance in normal human fasting serum that, like insulin, stimulated glucose oxidation and triglyceride synthesis in adipose tissue but that, unlike insulin, could not be extracted from plasma into acid-ethanol. In 1963, Froesch et. al. found that serum from guinea pigs immunized against insulin, suppressed insulin action in fat tissue, but it had no effect on Leonards’s insulin-like substance and so the term nonsuppressible insulin like activity (NSILA) was born.

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