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The sight or smell of a mouthwatering dish can be enough to trigger different processes in the body. Lior + Lone/Stocksy
  • The hormone insulin regulates blood glucose levels by helping glucose move into cells.
  • When someone sees or anticipates food, the pancreas releases insulin ready to process this glucose.
  • A new study has found that this early release is caused by an inflammatory response.
  • People with overweight and obesity have an excessive inflammatory response which impairs insulin secretion.
  • The findings suggest that targeting the inflammatory factor involved may improve the early insulin response in people with obesity.

Everyone is familiar with the sensation of the mouth watering in anticipation of food, but this is not the body’s only response. At the same time, the pancreas starts to release insulin, ready to deal with the influx of glucose into the blood.

This neurally mediated or cephalic phase response has been recognized for some time, but the mechanisms involved were unclear. Now, a study from the University of Basel has shown that a short-term inflammatory response is responsible for this early insulin release.

However, in people with overweight or obesity, an excessive inflammatory response during the cephalic phase can impair this insulin secretion.

“This study highlights the complexity of our individual metabolic responses to food, and why understanding chronic low-grade inflammation over time is key in addressing obesity.”

Prof. Tim Spector, professor of genetic epidemiology at King’s College London and co-founder of Zoe Ltd, a personalised nutrition company, speaking to Medical News Today.

The researchers identified that an inflammatory factor — interleukin 1 beta (IL-1β) — which is usually involved in the response to pathogens or tissue damage, is responsible for much of this early insulin secretion.

First, the researchers identified the role of IL-1β. They found that the sight, smell, or taste of food stimulates the release of IL-1β from microglia in the hypothalamus. This then activates the vagus nerve and increases the secretion of insulin that facilitates glucose uptake and metabolism after eating.

In their study, they placed mice that had been fasted overnight in a cage with a food pellet. The mouse was allowed to find the pellet and take a bite. Immediately after the first bite of food, the researchers took blood from the mouse for analysis.

The mouse blood samples showed no rise in glucose but had increased circulating insulin.

As a control, the researchers placed other mice in a cage with an inedible object that looked exactly like the food pellet. Blood taken from these mice showed no increase in insulin, indicating that real food was needed to stimulate the cephalic insulin response.

To test that IL-1β was responsible for the rise in insulin, they then injected mice with a neutralizing antibody against IL-1β before introducing them to the cage with food. These mice showed no increase in circulating insulin.

This led the researchers to conclude that IL-1β was mediating the cephalic phase insulin release (CPIR).

To investigate the implication of the finding for people with overweight or obesity, the researchers performed a secondary analysis of data from a previous meta-analysis on CPIR in people. The primary analysis found this insulin response was markedly reduced in those with overweight or obesity.

To test this finding, they reproduced the human data in the mouse model. After only two weeks on a high fat diet, mice no longer showed CPIR.

Study lead Prof. Marc Donath, chief of the Endocrinology, Diabetes & Metabolism Department at University Hospital Basel, told MNT why this might happen:

“Obesity and diabetes lead to chronic inflammation beyond which an acute sensory stimulation no longer has any effect. It’s like a marathon runner: after 42km, he can’t do a fast 100m race.”

Prof. Spector agreed: “The authors’ conclusions that cephalic insulin response, which causes insulin secretion before any food is consumed, such as when we see food or smell food, is inhibited in people with obesity due to chronic inflammation associated with obesity is likely to be part of the answer.”

“IL-1β […] signaling seems to be responsible for some of the vagus nerve stimulation that results in insulin secretion after sensory exposure to food, and a dysfunction in this signaling in people with obesity is likely impacting their cephalic insulin response,” he added.

Next, the mice were fed a high fat diet and injected with the anti-IL-1β antibody once weekly for 3 weeks, to prevent the release of IL-1β. The researchers subsequently detected insulin in the blood of these mice, showing they had a CPIR.

“With higher inflammation in obesity, and specifically adipose tissue inflammation, persistent high levels of circulating IL-1B is responsible for the dysfunction resulting in a lack of cephalic insulin response to sensory inputs.”

– Prof. Tim Spector

So, could this study have implications for the treatment of obesity and type 2 diabetes? Prof. Donath believes it might, given further research.

“IL-1β antagonism is being developed for the treatment of type 2 diabetes and its complications. A better understanding of the mechanism of action of IL-1β on insulin secretion could guide us in the development of clinical studies,” he told MNT.

This view was reinforced in an article in Cell Metabolism, which described the findings as: “an exciting avenue for developing IL-1β as a novel and potentially modifiable therapeutic target to correct autonomic dysregulation of CPIS [the cephalic phase of insulin secretion] in obesity.”