Targeting our second brain to fight diabetes

October 06, 2020

Since 2004, Claude Knauf (INSERM) and Patrice Cani (UCLouvain) have been collaborating on molecular and cellular mechanisms in order to understand the causes of the development of type 2 diabetes and above all to identify new therapeutic targets. In 2013, they created an international laboratory, 'NeuroMicrobiota Lab' (INSERM-UCLouvain), to identify links between the brain and intestinal bacteria.

Very quickly, they understood that the gut-brain axis plays a preponderant role in the regulation of sugar in the blood. When we eat, the gut (also called the 'second brain' owing to the neurons that compose it) contracts and digests food. Sugar and fat enter the body and their levels increase in the blood. Using this sugar and fat, the body then does its work or stores them. In a person with diabetes, this process malfunctions and the sugar level increases in abnormal proportions.

Taking a step further, the two researchers observed that the gut, when it digests, sends a signal to the brain, to find out what to do with the incoming fats and sugars. The brain then sends the message to various organs (liver, muscles, adipose tissue) to get ready to lower blood sugar and fat levels. In a diabetic individual, however, this mechanism doesn't work. Researchers have observed that the gut malfunctions and sends no signal to the brain. The cause is hypercontractility of the intestine, which interferes with communication with the brain. Suddenly, commands to get the sugar out of the blood no longer pass. The sugar remains, causing hyperglycaemia. The mechanism also impacts the action of insulin: no message means no insulin action, resulting in insulin resistance.

The researchers sought to understand this hypercontractility, by observing the differences in the constitution of the intestine as well as the action of prebiotics within the microbiota in 'normal' and 'diabetic' mice. They observed that a particular lipid was severely deficient in diabetic mice, but also in people with diabetes (although it's naturally present in the intestines of healthy patients). The team therefore tested the impact of the lipid on the use of sugars, on the contraction of the intestine and, ultimately, on diabetes. NeuroMicrobiota research team members Anne Abot and Eve Wemelle discovered the lipid is the key to restoring the use of sugar. It works by acting directly on the second brain.

Today, the team has discovered and understood how our gut bacteria (or gut microbiota) play an important role in altering the production of bioactive lipids, and from there to restore perfect communication between the gut and the brain. Hence some of these lipids are essential messengers which act on very precise targets in the second brain (enkephalins or opioid receptors). Treatment possibilities include modifying the body's production of such lipids, could or taking them orally. These avenues are under study.

Using the same approach, the INSERM-UCLouvain research team, contributed to the discovery of a new bioactive lipid that reduces intestinal inflammation. It is directly produced by certain gut bacteria, also identified in this study and therefore the two approaches, either the lipid or one or more bacteria, could serve as a therapeutic target.

One in three of the 150,000 humans who die every day is a victim of cardiovascular disease, according to WHO. Half the Belgian population is overweight and presents cardiovascular and type 2 diabetes risks. This UCLouvain and INSERM research could potentially have an impact on a large portion of the population.
-end-
To carry out this research, UCLouvain's Patrice Cani received funding from several sources including WELBIO, FNRS and the Baillet-Latour Fund.

Université catholique de Louvain

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.