Endocrine Abstracts

The endocrine cells of the gastrointestinal system are scattered amongst the mucosal cells and respond to luminal influences via projecting microvilli. They also respond to a rich neural supply through the submucous plexus. These two influences, luminal nutriments and local innervation, compete with control by circulating hormones and also nutriment concentrations. The gut endocrine cells are widely scattered down the mucosa (diffuse endocrine system) and their response is proportional to the length of gut stimulated. The same peptides are also present as neurotransmitters in the central nervous system, which led to study of their central actions. CNS GLP1 was found to inhibit gastric emptying through dorsal vagal complex in the brain stem. All the gut hormones also block appetite through various central mechanisms.

The world pandemic of obesity shortens life through many mechanisms and is also socially unhelpful. Eat less food, take more exercise, advice only works for some of us. Medication is also mostly ineffective and not free of side effects. Bariatric bypass surgery works. Although designed to produce malabsorption it actually doesn’t and acts by dramatically reducing long term appetite. Bypass halves cancer rates and causes remission in the majority of type 2 diabetics, through weight loss. Thinner you actually live longer. However, the procedure is risky, expensive and cannot be adjusted easily.

We identified the most important mechanism involved in gastric bypass was an increased release of the satiety inducing gut hormones, and embarked on a long journey to create a “medical bypass”. Thus, we developed analogues of the three main gut satiety hormones so they can be given weekly. In animals they produce massive weight loss and diabetes remission. We are now involved in phase 1 human trials of these agents. This programme has required considerable time and resources but could save a lot of life.