Growth hormone (GH) can generate insulin-like growth factor-I production, provided that the liver encounters portal insulin as a permissive factor that switches on the liver sensitivity for GH. This phenomenon is important for a proper insight into the pathophysiology of diseases as type 1 and 2 diabetes which differ in portal insulin levels. Also, acromegaly and obesity can be better understood when this effect of insulin on liver sensitivity for GH is taken into account. Moreover, as all of these factors seem to influence activity of the 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 (and 2), an extensive knowledge on the interplay between them is crucial as nowadays treatment options for obesity using the 11β-HSD1 are emerging. Copyright