Sir Edward Schafer, who was Professor of Physiology in Edinburgh, appears to have named insulin and described its actions.
He did so in a book, The Endocrine Organs, based on a lecture series he gave in California in 1913. In this book, published in 1916,5 he gave the hypothetical substance a name that stuck; what is more, with remarkable vision, he described its likely formation from activation of an inert precursor:
It must however be stated that it has yet to be determined whether the active substance is produced as such in the pancreas or whether it exists there as pro‐insuline which becomes elsewhere converted into the active autacoid.
Insulin was discovered 8 yr later by Banting and Best in 1921. The first patient was treated a year later in 1922 and pro‐insulin was discovered (and re‐named) more than 50 yr later by George Steiner of the University of Chicago in 1967.
As Schafer hypothesized, insulin has two classes of action: (i) excitatory (autacoid), for example stimulating glucose uptake and lipid synthesis; and (ii) inhibitory (chalone), for example inhibiting lipolysis, proteolysis, glycogenolysis, gluconeogenesis and ketogenesis. These dual actions are illustrated in Fig. 1, where insulin’s well recognized action in stimulating lipogenesis from glucose (in rat adipocytes) is illustrated.6 What perhaps is less well known is insulin’s simultaneous inhibitory action on lipolysis. It is quite clear from Fig. 1 that both these actions occur simultaneously over the same concentration range. They are both mediated through the same cell membrane receptor.
How then does insulin lower the blood glucose in diabetes?
Again this question is simple to answer and, by now, the answer will not be surprising. The use of tracer glucose infusions has shown not only that hyperglycaemia in the face of insulin deficiency is the result of over‐production of glucose by the liver but also that insulin infusion lowers blood glucose by inhibiting hepatic glucose production. Indeed, rather than stimulating glucose uptake in tissues such as muscle, insulin in fact reduces glucose uptake. This is because the main factor driving glucose uptake is the ‘mass action’ effect of hyperglycaemia and the concentration gradient between the extracellular and intracellular glucose concentrations. Glucose transporters are not rate limiting under these conditions, even in the face of severe insulin deficiency.