Breaking News
May 26, 2018 - Study links cell size with commitment to division
May 26, 2018 - Researchers develop new, rapid blood test to detect liver damage
May 26, 2018 - Researchers discover cascade of immune processes linked to poor outcomes in aggressive breast cancer
May 26, 2018 - New research will use mathematics to solve mysteries in cell biology
May 26, 2018 - Mice remain slim on burger diet
May 26, 2018 - BMC receives $13.5 million award to test methods for delivering childhood anxiety treatment
May 26, 2018 - ‘Right to Try Act’ will not benefit terminally-ill patients
May 26, 2018 - Study reveals novel statistical algorithm to identify potential disease genes
May 26, 2018 - Two genes play vital roles in malignant brain cancer
May 26, 2018 - Study explores link between groundwater lithium and diagnoses of bipolar disorder, dementia
May 26, 2018 - Researchers reveal stimulatory effects of myelin on young neural cells
May 26, 2018 - Small part of cellular protein that helps form long-term memories also drives neurodegeneration
May 26, 2018 - Four-legged friends can have heart issues, too
May 26, 2018 - Scientists create small, self-contained spaces inside mammalian cells
May 26, 2018 - Better Social Support Network Protects Black Men Against HIV
May 26, 2018 - National Heart, Lung, and Blood Institute (NHLBI)
May 26, 2018 - Burnout, depression can affect ophthalmology residents, study finds
May 26, 2018 - Latinos and African Americans more likely to experience serious depression than Whites
May 26, 2018 - Data from past epidemic could help improve response to future Ebola outbreaks
May 26, 2018 - Researchers provide insight into how the memory molecule limits brain plasticity
May 26, 2018 - OSU biologist describes ‘restoration ecology’ approach toward patient health
May 26, 2018 - New approach to study brown fat could aid in finding treatments for obesity
May 26, 2018 - Could More Fish in the Diet Boost Sex Lives and Fertility?
May 26, 2018 - NTU Singapore and SERI invent new scope to diagnose glaucoma
May 26, 2018 - Cancer cells co-opt pain-sensing ‘neural channel’ to increase tolerance against oxidative stress
May 26, 2018 - Study uncovers why pesticide exposure increases Parkinson’s disease risk in some people
May 26, 2018 - Study finds link between lead exposure and fertility rates
May 26, 2018 - Delivery of standardized diabetes care could help achieve equitable health outcomes for all patients
May 26, 2018 - FDA authorizes marketing of OsteoDetect software for detecting wrist fractures
May 26, 2018 - Children and adolescents growing up in extreme societal conditions more likely to resort to violence
May 26, 2018 - New study puts forth most comprehensive tree of life for malaria parasites
May 26, 2018 - UVA researchers establish new guidelines for explorers of the submicroscopic world inside us
May 26, 2018 - Princeton Instruments and C-SOPS announce collaboration on innovative pharmaceutical technology
May 26, 2018 - New research shows why babies need to move in the womb
May 26, 2018 - UK steps forward to tackle global antimicrobial resistance
May 26, 2018 - CRISPR-Cas9-based strategy allows researchers to precisely alter hundreds of different genes
May 26, 2018 - Novoheart announces next generation of ‘Human heart-in-a-jar’ technology for advanced drug discovery
May 26, 2018 - UT Southwestern-led researchers find new way to determine prognosis of invasive kidney cancer
May 26, 2018 - Researchers develop film to prevent bacteria from growing on dental retainers and aligners
May 26, 2018 - Mobile health intervention for people with serious mental illness as effective as clinic-based treatment
May 26, 2018 - Vaginal estradiol tablets outperform moisturizers when treating vulvovaginal problems
May 26, 2018 - Researchers call for new genetic tests for congenital diseases
May 26, 2018 - KHN’s ‘What the Health?’ Campaign promises kept, plus ‘nerd reports’
May 26, 2018 - AARDA collaborates with Allegheny Health Network and new AHN Autoimmunity Institute
May 26, 2018 - Lung-on-a-chip technology could streamline drug-testing for pulmonary fibrosis
May 26, 2018 - Researchers work together to solve mystery of motor neuron death in ALS patients
May 26, 2018 - Study finds early antibiotic initiation for majority of premature infants
May 26, 2018 - New environmental monitoring project finds increased numbers of deer ticks in Southern Indiana
May 26, 2018 - Pediatricians Should Advocate for Life Support Training
May 26, 2018 - Cannabidiol significantly reduces seizures in patients with severe form of epilepsy
May 26, 2018 - Allergies can have serious, far-reaching consequences on adolescents
May 26, 2018 - Scientists develop lab-based system to study mechanisms of common liver disease
May 25, 2018 - New guidelines may help pathologists to more accurately classify and diagnose invasive melanoma
May 25, 2018 - Immune cells promote lung cancer metastases by forming clots in tumors, study finds
May 25, 2018 - Can Excess Weight in Toddlers Cause Brain Drain?
May 25, 2018 - Studying insight
May 25, 2018 - Researchers reveal potent new mechanism of action for treatment of IBD
May 25, 2018 - Study shows lack of follow-up care for patients with concussion
May 25, 2018 - Study establishes the importance of haploid cells
May 25, 2018 - Coveted BMJ award bestowed on The Clatterbridge Cancer Center
May 25, 2018 - AACN outlines evidence-based protocols and clinical strategies to manage alarms
May 25, 2018 - Origami inspires researchers to develop new solution for tissue regeneration
May 25, 2018 - Melorheostosis – Genetics Home Reference
May 25, 2018 - Non-addictive pain medication changing therapy for substance use disorders
May 25, 2018 - Delayed lactate measurements in sepsis patients increase risk of in-hospital death
May 25, 2018 - Researchers identify novel epigenetic mutations as cause of neurodevelopmental, congenital disorders
May 25, 2018 - UD researchers examine connection between DNA replication in HPV and cancer
May 25, 2018 - Researchers identify neurons that play key role in aggressive behavior
May 25, 2018 - Snail’s eye inspires new type of RIOCATH urinary catheter
May 25, 2018 - Russian researchers develop high-tech device-transformer for ultrasound examination
May 25, 2018 - Researchers discover unexpected chemosensor pathway for predator odor-evoked innate fear behaviors
May 25, 2018 - Researchers build 3-D printer that offers sweet solution to making detailed structures
May 25, 2018 - Nearly one in three people know someone addicted to opioids
May 25, 2018 - Research suggests link between faulty gene, alcohol, and heart failure
May 25, 2018 - New findings could help fine-tune treatment for cancer patients
May 25, 2018 - New cancer treatment approach targets specific sugar receptors
May 25, 2018 - Skin responsible for uptake of cancer-causing compounds during barbecuing than lungs
May 25, 2018 - Early-onset cannabis use linked to further drug abuse problems
May 25, 2018 - Covered California takes aim at hospital C-section rates
May 25, 2018 - FDA Approves Palynziq (pegvaliase-pqpz) for the Treatment of Adults with Phenylketonuria
UNIGE scientists unravel key role played by the liver in onset of type-2 diabetes

UNIGE scientists unravel key role played by the liver in onset of type-2 diabetes

image_pdfDownload PDFimage_print

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, and 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. Today, scientists from the University of Geneva (UNIGE) unravel 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 scientists open the door to potential new therapeutic strategies. These results can be read in Nature Communications.

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”, he adds.

No diabetes without PTPR-γ

To test their hypothesis, the scientists modified the levels of PTPR-γ expression in mice, by either supressing, 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 this 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 two-fold overexpression in the liver (mimicking the natural pathophysiology of obesity) was sufficient to cause insulin resistance.

A new therapeutic target?

The metabolic functions of this protein were never characterized; this discovery therefore opens the door for potential new therapies. Previous studies had already studied PTP proteins in search for diabetes treatments, unfortunately 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.

From bedside to the lab, and back: how 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. 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 1 in 11 adults globally, or 422 million people.”

Tagged with:

About author

Related Articles