Type 2 diabetes starts in liver, find University of Geneva scientists

85ea089c-249f-457c-97bb-54a2d9ea5e22articleimage.jpg

28 Nov 2017 --- Scientists from the University of Geneva (UNIGE) in Switzerland have unraveled the factors linking obesity and insulin resistance, as well as the key role played by the liver in the onset of the disease. By deciphering how the protein PTPR- γ – which is increased in the context of obesity – inhibits insulin receptors located at the surface of liver cells, the researchers’ findings in Nature Communications open the door to potential new therapeutic strategies.

Among the detrimental effects of obesity is the risk of developing Type 2 diabetes. Even though the strong links between obesity and Type 2 diabetes are well known, the cellular and molecular mechanisms were so far poorly understood, UNIGE points out.

Affecting as many as 650 million people worldwide, obesity has become one of the most serious global health issues. Among its detrimental effects, it increases the risk of developing metabolic conditions, primarily Type 2 diabetes. If the strong links between obesity and Type 2 diabetes are well known, the cellular and molecular mechanisms by which obesity predisposes to the development of insulin resistance were so far poorly understood.

Protein provides key to insulin issues
By deciphering how the protein PTPR-γ, which is increased in the context of obesity, inhibits insulin receptors located at the surface of liver cells, the scientists have opened the door to potential new therapeutic strategies.

The expansion of fat cells, a characteristic of obesity, leads to an increase in inflammatory signals that have effects on the liver as well as on several other organs. Obesity-induced inflammation triggers the activation of a transcription factor called NF-kβ, which seems to be instrumental in the development of diabetes.

But what are the exact cellular and molecular mechanisms at stake and how could they lead to new therapeutic strategies? “To answer these questions, we focused on a protein called PTPR-γ (for Protein Tyrosine Phosphatase Receptor Gamma), which is a target of NF-kβ”, explains Professor Roberto Coppari, Coordinator of the UNIGE Faculty of Medicine Diabetes Centre.

“We first examined various human cohorts: these human studies indicated that PTPR-γ content in liver increases upon inflammation, an effect that could directly affect insulin receptors by inhibiting insulin action,” Coppari adds.

No diabetes without PTPR-γ
To test their hypothesis, the scientists modified the levels of PTPR-γ expression in mice, by either suppressing, normally expressing or overexpressing it, and observed the effect on insulin resistance.

“The mice totally lacking PTPR-γ, when put on a high-calorie diet, did develop obesity. But they did not show any sign of insulin resistance and seemed to be entirely protected from diet-induced diabetes,” explains Xavier Brenachot, a researcher at UNIGE Faculty of Medicine and first author of the study. The scientists also administered lipopolysaccharide, a toxin pertaining to certain bacteria of the gut microbiota associated with obesity and insulin resistance. Once again, the animals lacking PTPR-γ did not develop insulin resistance.

To fine-tune their analysis, Roberto Coppari and his colleagues reconstituted the expression of PTPR-γ at normal levels, but only in hepatocytes (liver cells). The mice were again prone to insulin resistance, indicating the pivotal role of the liver. Moreover, a twofold overexpression in the liver (mimicking the natural pathophysiology of obesity) was sufficient to cause insulin resistance.

Potential new therapeutic target
The metabolic functions of this protein were never characterized; this discovery therefore opens the door for potential new therapies, UNIGE reports. Previous studies had already studied PTP proteins in search for diabetes treatments to no avail.

However, contrary to some of its family members that are intracellular, the protein identified in Geneva is located on the cell membrane. It is therefore of much easier access for therapeutic molecules. Interestingly, the very form of this protein allows for potential inhibition strategies: when two independent PTPR-γ molecules are brought together by a ligand, they cannot act any more.

The researchers are now working on identifying the endogenous ligand produced by the body, or on developing molecules that could mimic its function.

Translational research shapes tomorrow’s medicine
“This study would not have been possible without the UNIGE Faculty Diabetes Centre, established in 2015 to enhance interactions between clinical and basic researchers,” indicates Roberto Coppari.

“Indeed, our research started with clinical observations made by Prof. Francesco Negro – also a member of UNIGE Faculty Diabetes Centre – at the University Hospitals of Geneva,” Coppari adds. “We now hope that our pre-clinical and clinical results will in turn be translated into clinical progress and contribute to a better management of Type 2 diabetes that, today, affects one in 11 adults globally, or 422 million people.”

To contact our editorial team please email us at editorial@cnsmedia.com

Related Articles

Nutrition & Health News

Labeling debate: Health labels may deter people from buying sugary drinks

25 May 2018 --- Young adults are less likely to buy sugar-sweetened beverages that include health labels, particularly those with graphic warnings about how added sugar can lead to tooth decay, obesity and Type 2 diabetes, according to research presented at this year's European Congress on Obesity (ECO) in Vienna this week. 

Nutrition & Health News

Weekly Digest: Arla expands fiber yogurt range, probiotics may reduce hay fever symptoms

25 May 2018 --- This week in nutrition news, Arla revealed a new addition to its fiber yogurt range, hoping to boost the UK's daily fiber intake. In research news, probiotic formulations were found to have positive effects on hay fever symptoms, while following a diet high in antioxidants may protect people from the adverse effects of pollution. Furthermore, researchers have made steps in understanding the link between a mothers nutrition during pregnancy and the child's growth, and a study undercovered that consumers are more likely to order unhealthy options when dining out amid louder, ambient music.

Nutrition & Health News

Avoid the snacks? To manage weight, timing of protein supplements matters

25 May 2018 --- Protein supplementation is finding its way into an ever-increasing range of formats, with on-the-go snacks and “bite-size” in particular seeing tremendous growth. However, new research by nutrition experts at Purdue University has shown that people looking to manage their weight with strength-training and protein supplements should consume their supplementation during a meal. 

Nutrition & Health News

calocurb: 100 percent plant-based weight management product launched in US market

25 May 2018 --- New Zealand-based nutrition and e-commerce company calocurb has launched its 100 percent plant-based, non-GMO weight management supplement into the US market. The product is designed to curb cravings and reduce calorie intake by around 20 percent at meal or snack time.

Nutrition & Health News

UK sugar reduction efforts fail to reach initial target, industry urged to step up or face tax

23 May 2018 --- The first assessment of the UK government’s sugar reduction program has unveiled failings by industry to reduce sugar in the first year by 5 percent, leading to calls of a sugar tax on sweet treats. The results of the first year have been roundly criticized in the media and described as “hugely disappointing” after Public Health England data revealed that sugar was cut in some categories – sweet spreads and sauces, yogurts and fromage frais and breakfast cereals – while other food groups have fallen short.

More Articles
URL : http://www.nutritioninsight.com:80/news/type-2-diabetes-starts-in-liver-find-university-of-geneva-scientists.html