The discovery of peptides used for the treatment of diabetes/obesity: A personal journey.

The aim of this personal reminiscence is to acquaint the reader with seminal workwork carried out in 1960 s and 1970 s that made possible the subsequent development of highly effective long-acting GLP-1R agonists and GLP-1R/GIPR co-agonists that are now in clinical practice for the treatment of Type 2 diabetes and obesity. The article highlights the particular contributions of the author's collaborators Ellis Samols and Desmond Turner in elucidating the nature and significance of gut glucagon-like immunoreactivity (enteroglucagon) and GIP. The potent incretin GLP-1(7-36)amide identified in the 1980 s met the criteria for a glucagon-like-substance with incretin like properties postulated to exist by Samols and others in 1966.

The early history of GIP 1969-2000: From enterogastrone to major metabolic hormone.

This paper describes the early history of Gastric Inhibitory Polypeptide, better referred to simply as GIP, from its isolation by purification from a crude preparation of CCK-PZ (cholecystokinin/pancreozymin) to its recognition as a key play in the pathogenesis of obesity and other metabolic disorders far removed from the enterogastrone properties by which it was originally identified. Augmentation of glucose mediated insulin release, the incretin effect, was discovered soon after GIP was first isolated and only much later was its important role in the pathogenesis of obesity, through mechanism other than its insulin secretion, appreciated. Immunoassay - the method by which the concentration of GIP was measured in plasma until quite recently - was found to be flawed and to depend upon which specific epitope of the hormone an assay detected.

The early history of GIP 1969-2000: From enterogastrone to major metabolic hormone.

This paper describes the early history of Gastric Inhibitory Polypeptide, better referred to simply as GIP, from its isolation by purification from a crude preparation of CCK-PZ (cholecystokinin/pancreozymin) to its recognition as a key player in the pathogenesis of obesity and other metabolic disorders far removed from the enterogastrone properties by which it was originally identified. Augmentation of glucose mediated insulin release, the incretin effect, was discovered soon after GIP was first isolated and only much later was its important role in the pathogenesis of obesity, through mechanism other than insulin secretion, appreciated. Immunoassay - the only method by which the concentration of GIP was measured in plasma until quite recently - was found to be flawed and to depend upon which specific epitope of the hormone an assay detected.

Rebirth of the Incretin Concept: Its conception and early development.

This paper describes the resurrection of the Incretin Concept in the early 1960s. It began with the more or less simultaneous discovery by three groups working independently in London. Dupre demonstrated that secretin given intravenously with glucose increased its rate of disappearance from the blood, McIntyre and co-workers established that hyperglycaemia evoked by oral glucose stimulated more insulin secretion than comparable hyperglycaemia produced by intravenous glucose and Marks and Samols established the insulinotropic properties of glucagon.

Hypoglycaemia and automatism.

Cognitive impairment unattended by subjective symptoms or objective signs is an uncommon but important consequence of hypoglycaemia. It can lead to a condition in which a patient behaves as an automaton in a manner totally alien to their usual personality and of which they have no recollection when their blood glucose level is restored to normal. It can cause a wide range of criminal behaviour, although the commonest offences relate to a loss of control, for example driving offences.

Forensic aspects of insulin.

Insulin or, more appropriately, hypoglycaemia gives rise to a wide variety of interactions with the law. In most cases its role is not seriously open to question occasionally however, it is. This is especially true of situations in which insulin is suspected of having been used inappropriately or maliciously.

Murder by insulin: suspected, purported and proven-a review.

Murder by insulin-whether attempted, suspected or proven-is rare. Only 66 cases worldwide could be found for this review. A conviction was secured in 31 cases and additional weapon was employed in 11.

Human obesity: its hormonal basis and the role of gastric inhibitory polypeptide.

Obesity is an abnormal expansion of the adipose organ and is a pathophysiological response to an imbalance between energy intake and energy expenditure. It is the result of a large number of diverse factors involving heritable and environmental characteristics. A simple definition of obesity is difficult and unsatisfactory and its age dependency has largely been ignored.

The metabolic syndrome.

Prevention of disease rather than its alleviation or cure has always been the aim of healthcare professionals. While this goal has been achieved for many infectious diseases through improvements in hygiene and vaccination, as well as for acute deficiency diseases such as scurvy, less progress has been made with chronic diseases. These are increasing as the population ages.

False-positive immunoassay results: a multicenter survey of erroneous immunoassay results from assays of 74 analytes in 10 donors from 66 laboratories in seven countries.

Background: Analytical interference in immunoassays can produce serious errors, but it is generally considered rare with modern analytical systems.

Method: Blood was collected from 10 donors with illnesses known to be associated with rheumatoid factor. Immunoassays for 74 analytes were performed in 66 clinical laboratories.