Introduction

In the 1920s and 1930s the landmark work of Bernardo Houssay established that extracts from the pituitary gland had profound effects on glucose metabolism. These studies showed that removal of the pituitary gland increased the sensitivity to insulin in normal animals and diminished the intensity of diabetes in depancreatized animals, and that administration of pituitary extracts decreased insulin sensitivity and could lead to diabetes (Houssay, 1936; Young, 1940). At the same time it was observed that anterior lobe extracts are ketogenic and growth promoting and recognized that these actions were caused by distinct hormones (Shipley & Long, 1938). The notion that the diabetogenic, ketogenic and growth promoting effects of secretion from the pituitary were caused by a single hormone was first advanced by Shipley & Long (1938). Following on from the purification of human growth hormone (GH), a number of important studies showed that exposure to large amounts of pituitary extracts of GH in normal, GH-deficient and diabetic human volunteers stimulated lipolysis, which led to hyperglycaemia (Beck et al., 1957; Ikkos et al., 1958b; Raben and Hollenberg, 1959; Henneman & Henneman, 1960). It was also reported that GH, when perfused locally through the brachial artery, consistently caused acute inhibition of muscle glucose uptake in the forearm in normal subjects (Zierler & Rabinowitz, 1963; Rabinowitz, Klassen & Zierler, 1965; Fineberg & Merimee, 1974). The next major break-through was the identification of insulin-like growth factors(IGFs) and the subsequent moulding of the concept that GH regulated IGF-I synthesis accounts for a large proportion of the anabolic impact of GH (Froesch et al., 1996).