Direct gut to pancreas neuronal communication in the regulation of metabolism

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What you eat plays a major role in health and ill health. Every day the body consumes foods which are broken down in the gut into a complex mixture of molecules. These molecules are sensed in the gut to modulate metabolic functions. They help to regulate digestion but also body wide processes, including how the body regulates glucose, and how it processes fat and protein. New scientific tools are for the first time allowing us to understand how these food components affect metabolism and health on a molecular level. The pancreas is a particularly important metabolic organ, with critical roles in digestion, and in carbohydrate, fat and protein metabolism. Maintaining good pancreatic function is vital to maintaining health across the life course. The pancreas sits next to the upper part of the small intestine, which is called the duodenum. Almost fifty years ago it was discovered that there are neurons that originate in the wall of the duodenum which extend to the pancreas, suggesting that the gut could signal directly to the pancreas via this pathway to rapidly adjust pancreatic function and metabolism in response to food. However, subsequently, these neurons have been little studied. Our pilot data shows that a subpopulation of these neurons is involved in the pathway by which specific fats can improve the metabolic response to glucose. However, there are many other neurons in this pathway which are almost completely uncharacterised. We will map the neurons signalling from the gut to the pancreas in a mouse model, and establish the food-related molecules that regulate their function. We will manipulate these neurons in mice to determine the effects they have on metabolism, and whether they can synchronise the activity of different parts of the pancreas to have even greater effects on the body. These studies will determine whether in the future these neurons can be usefully targeted by special diets to improve long term health.