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Robert Turner (1938–1999) was a remarkable man. Although he is perhaps best known for the groundbreaking UK Prospective Diabetes Study (UKPDS), the breadth and depth of his contributions to diabetes research are remarkable. It is a privilege for us, just a few of his many close friends and colleagues, to be able to review his contributions as a scientist and to remember him as a unique human being. His seminal discoveries spanned three broad areas of diabetes research—namely, the physiology of insulin secretion, the etiopathogenesis of type 2 diabetes, and the clinical management of diabetes. In all of these areas, his combination of intense curiosity, intelligence, indefatigability, and passion for improved patient care led to landmark discoveries that have withstood the test of time. Robert was a medical student in Cambridge and undertook his clinical training and MD research at the Middlesex Hospital in London with Dr. John Nabarro; his thesis was entitled “Plasma Glucose Control of Insulin Secretion in Man.” The interactions of insulin and glucose occupied much of his physiological interests in those early days. His early mathematical examination of insulin delivery rate (1) was rediscovered many years later, and the concepts of feedback control were brilliantly exemplified with fish insulin, which cleared glucose but did not cross-react with insulin assays, thus allowing endogenous insulin to be assayed (2). In these early days, through exposure to scientists such as Roger Ekins, a pioneer of immunoassay, Robert was discovering that lab-based techniques were the window into complex in vivo interactions. He moved to Oxford in the early 1970s and began to develop the Diabetes Research Laboratory (DRL), which, from humble beginnings, became one of the world's leading centers for diabetes research. The DRL began to hum with activity as the charcoal separation assay developed when Robert was working with …

In fish, the structural and functional characteristics of insulin and IGF-I receptors have been well studied. Current evidence indicates that all gnatostome animals, from fish to mammals, contain separate insulin and IGF-I molecules and specific receptors for insulin and IGF-I. However, qualitative differences in the functional aspects of insulin and IGF-I receptors among vertebrate species can account for variations in the biological activity of insulin and IGF-I. In this paper we will focus on the functional evolution of the insulin and IGF-I receptors in vertebrates and on the appearance of the unrelated IGF-II receptors.

The physiologically responses to hypoglycaemia induced by fish insulin were studied in nine tetraplegic subjects with physiological complete cervical spinal cord transection between C4 and C8. During hypoglycaemia there was a reduction in both systolic and diastolic blood pressure unlike in normal subjects. This was accompanied by a rise in heart rate. The normal rise in plasma adrenaline levels did not occur. Plasma human insulin levels were suppressed. The usual neuroglycopenic symptoms accompanying hypoglycaemia did not occur in the tetraplegics.

About 90% of Aburazame landed on our fish-markets are found 60-80cm. in body length, and the average weight of their pancreas is 5g. (Tab. I A, B and Fig. 1). As the pancreas contains only little fat (Tab. II), insulin can be simply extracted from it after Dudley's method. We can obtain 17.5 units (estimated by Toronto method) of insulin per head, (Tab. III).

Under conditions in which insulin molecule has a maximal positive charge, comparison of paper chromatographic and paper electrophoretic behaviors was performed between fish and beef insulins. In 33 per cent acetic acid fish insulin migrates faster than beef insulin, whereas it shows lower Rf when is chromatographed using acetic acid-butanol-water (1:3:4) solvent.

In the present study, we attempted to define possible subpopulations of antibodies which theoretically could be directed against evolutionarily conserved regions of the insulin molecule in sera from insulin-treated diabetic patients using a variety of labelled and unlabelled insulins which differ widely in structure but are very similar in functional properties. Ten high titre human insulin antisera from patients treated with mixed beef-pork insulin were examined. All sera were found to bind 125I-pork insulin better than labelled chicken insulin which bound better than labelled fish insulin. Detailed studies were conducted with four of the antisera using the pork and fish tracers. With two of the antisera, a subpopulation of antibody could be detected with 125I-fish insulin which had similar affinity for both fish and pork insulin, but reacted much less well with guinea pig insulin and the desoctapeptide derivative of porcine insulin. Based on the known properties of these four insulins, the data provide suggestive evidence consistent with the hypothesis that there are subpopulations of antibodies recognizing regions on the insulin molecule that are well conserved, possibly the region involved in the formation of insulin dimers or receptor binding.