New study reveals role of gut hormone in insulin and blood sugar levels

An Australian and a British researcher have published the results of a breakthrough study expected to transform traditional thinking about the digestive process and possibly lead to new treatments for Type 2 diabetes and other diseases.

Professor Herbert Herzog from Sydney’s Garvan Institute, in collaboration with Professor Helen Cox from King’s College London, have found that the hormone, gut peptide YY (PYY) - released when we eat and involved in telling us when we are full - also determines the speed at which food is digested and nutrients are absorbed into the blood. It also helps regulate our insulin and blood sugar levels.

Conventional wisdom is that eating raises glucose levels in the blood, which in turn triggers the release of insulin from the pancreas to assist cells to absorb the glucose. However, this new research, just published in the journal Cell Metabolism demonstrates that things are a lot more complicated than that.

“We show the central role that PYY plays inside the gut, orchestrating a cascade of other events that ultimately affect the energy balance of the entire body,” said Professor Herzog.

Endocrine cells in the human gut hold PYY and other peptides such as glucagon-like peptide 1 (GLP-1). Receptors like GPR119 on the surface of these cells sense nutrients inside the gut, helping them to regulate digestion.

So called ‘fatty acid amides’, one of the products from the breakdown of food, activate the GPR119 receptors, causing them to co-release PYY and GLP-1. The peptides subsequently bind to various receptors on the gut lining that modulate nutrient and electrolyte absorption, leading eventually to the absorption of nutrients and electrolytes into the blood stream.

“We identify a double-barrelled mechanism where the fatty acid amides present inside the gut or the blood can stimulate the endocrine cell receptor,” said Professor Cox. “It’s important to note that the receptor is stimulated more when glucose is present.”

“GPR119 stimulation leads to release of PYY with GLP-1 which act locally to enhance nutrient and electrolyte absorption within the gut wall before going into the bloodstream.”

The affects of GLP-1 on glucose tolerance have been known for some time, and there are a number of drugs on the market designed to stimulate the production of GLP-1 or to extend its life span in the blood.

“Our novel finding is that the process actually goes through the PYY system, not only through GLP-1 as thought previously,” said Professor Herzog. “We believe that up until now the role of PYY has been underestimated. By showing its true importance, we highlight its potential, as well as that of GPR119, as a therapeutic target for people with metabolic disorders, including Type 2 diabetes.”

Professor Cox noted that a GPR119 agonist would have greater therapeutic benefits by activating both PYY and GLP-1 release, adding that GPR119 agonists are already in clinical Phase 1 trials.