Error in protective response post-meal may lead to diabetes, says Swiss team

Malfunction of the inflammatory response after a meal could be a cue for metabolic disorders such as diabetes as doctors identify its differing roles in dealing with pathogens and excess food intake.

Findings from the Swiss study have identified the protective mechanism by which the inflammatory response deals with bacteria ingested after each meal.

This short-term inflammatory response also plays a significant role in sugar uptake and eventual activation of the host’s immune response.

Further experiments by the researchers revealed that prolonged activation of the immune system by over-nutrition could eventually promote the development of metabolic diseases.

In understanding the relationship, it could be called upon to help resolve the challenge of nutrients and microorganisms related to food intake, particularly those prone to over eating or even malnourishment.

According to the study team, a healthy supply of nutrients means the immune system is able to deal with alien bacteria.

In contrast when there is a lack of nutrients, calories must be conserved for important life functions at the expense of an immune response.

This could partially explain why infectious diseases occur more frequently in times of famine.

March of the macrophages

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Several studies have shown that food intake induces a mild inflammatory response to accompany insulin secretion. ©iStock

Led by Professor Marc Donath from the University Hospital Basel, the team began looking at the immune cells known as macrophages.

They noticed that these cell numbers increased within the intestine during the ingestion of a meal.

These macrophages then released a substance called IL-1beta, a protein that plays a key role in the inflammatory response.

It is also involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis (cell death).

IL-1beta, in turn promotes the production of insulin in pancreatic beta cells creating a feedback loop that causes the macrophages to increase IL-1beta production.

The team found that insulin and IL-1beta formed an effective relationship to regulate blood sugar levels.

A healthy IL-1beta amount ensured that the immune system was supplied with glucose and thus remained in an active state.

“Both insulin and IL-1β regulated whole-body glucose disposal by promoting glucose uptake in muscle and fat, and fuelled the immune system by stimulating the uptake of glucose into the immune-cell compartment,” the researchers commented.

Self-amplification of the system was limited by normalisation of glycaemia.”

Mechanism of action

The team proposed a mechanism that concerned the increased plasma concentrations of insulin noted in Type 2 diabetics.

They thought this may drive and sustain the inflammatory state in macrophages and might therefore contribute to the chronic low-grade inflammation associated with metabolic diseases.

In support of that, they referenced a study with mice which exhibited a deficiency in the INSR gene that provides instructions for making an insulin receptor.

Here the team found this defect provided protection against metabolic inflammation and insulin resistance.

Source: Nature Immunology

Published online ahead of print: doi:10.1038/ni.3659

“Postprandial macrophage-derived IL-1 stimulates insulin, and both synergistically promote glucose disposal and inflammation.”

Authors: Marianne Böni-Schnetzler et al.