New insights into the genetic basis of a rare type of diabetes in babies have uncovered a biological pathway that is fundamental to insulin production by pancreatic cells, and which could boost research into new treatments for more common forms of diabetes. An international research team led by scientists at the University of Exeter, the Universit Libre de Bruxelles, and the University of Helsinki, used genome sequencing to reveal that a group of babies with shared clinical features, including the development of diabetes soon after birth, all had genetic changes in the YIPF5 gene, which is involved in cell trafficking from the endoplasmic reticulum (ER) to the Golgi. The team then combined stem cell research and CRISPR gene editing to show that this gene is essential for the function of the cells that produce insulin.
The research demonstrated how the genetic changes result in high levels of stress within the cells, causing cell death, and also showed, for the first time, that YIPF5 gene function is essential for neurons and insulin-producing cells, but appears to be dispensable for the function of other cells.
Co-study lead, Elisa De Franco, PhD, from the University of Exeter, said, This study highlights the importance of gene discovery to further our understanding of fundamental mechanisms in biology. In this case, our research has resulted in the identification of a gene essential for both insulin-producing cells and neurons, highlighting a biological pathway we previously did not know was so fundamental for insulin-producing cells. This has the potential to open new avenues of research and ultimately result in a better understanding of how other types of diabetes develop.
De Franco and colleagues reported on their findings in the Journal of Clinical Investigation (JCI), in a paper titled, YIPF5 mutations cause neonatal diabetes and microcephaly through endoplasmic reticulum stress.
Neonatal diabetes develops before the age of six months, and is caused by reduced numbers of insulin-producing pancreatic cells, or impaired cell function, the authors explained. Previous research has found that neonatal diabetes is most likely caused by a mutation in a single gene, rather than presenting as an autoimmune type 1 form of the disease. To date, 30 genetic causes have been described, which account for 82% of cases, the team noted. Many patients with neonatal diabetes also have neurological symptoms, which is not surprising, the researchers continued, as cells and neurons have many genes and cellular functions in common. Pathogenic variants in 11 genes are already known to cause neonatal diabetes with neurological features, and one of the pathways known to be crucial for the function of both cells and brain cells is the endoplasmic reticulum stress response. In fact, Pathogenic variants in eight genes known to be involved in regulating the ER stress response have been found to caused diabetes (ranging from neonatal to adolescent/adult-onset diabetes), often associated with neurological features, the scientists pointed out.
To further study which genes are key to the function of insulin-producing cells, in the context of neonatal diabetes, the research team studied the genetics of almost 190 patients from all over the world who developed diabetes soon after birth. Identifying the genes causing syndromic forms of neonatal diabetes that include neurological features can highlight pathways important for development and function of -cells and neurons, giving insights into the pathogenesis of more common diseases, they noted. The results identified six babies who had neonatal diabetes and other very similar clinical featuresincluding epilepsy and microcephalyand who all exhibited mutations in the YIPF5 gene.
Researchers at the Universit Libre de Bruxelles and the University of Helsinki then carried out a series of studies in insulin-producing cells and in stem cells to try to understand the function of YIPF5 in the insulin-producing cells. We used three human cell models (YIPF5 silencing in EndoC-H1 cells, YIPF5 knockout and mutation knockin in embryonic stem cells, and patient-derived induced pluripotent stem cells) to investigate the mechanism through which YIPF5 loss of function affects cells, the investigators explained. Their results showed that when the gene was lacking, or had the same mutations as those found in the neonatal diabetes patients, the insulin-producing cells couldnt function normally to produce enough insulin. And an attempt to cope with this malfunction the cells activated stress mechanisms, which ultimately resulted in cell death. YIPF5 deficiency reduces -cell survival by enhancing the ER stress response and sensitizing human -cells to ER stress-induced apoptosis, they commented.
Co-senior study author Timo Otonkoski, from the University of Helsinki, explained, Using the CRISPR gene scissor DNA-editing technology we could correct the patient mutation in stem cells in order to fully understand its effects. The combination of gene editing with stem cells provides powerful new tools for the study of disease mechanisms. Colleague and co-senior author, Miriam Cnop, PhD, from the Universit Libre de Bruxelles, continued, The possibility to generate insulin-producing cells from stem cells has given us the possibility to study what goes wrong in cells from patients with this rare form and also other types of diabetes. It is an extraordinary disease-in-a-dish model to study mechanisms of disease and test treatments.
The teams study results offer new insights into which cellular steps are important for making insulin, and for maintaining the function of insulin-producing cells in the pancreas. This insight could help researchers develop better therapies to treat patients with common types of diabetes that affect 460 million people worldwide.
To the best of our knowledge, this is the first report of mutations in a gene affecting ER-to-Golgi trafficking resulting in diabetes by increasing -cell ER stress, uncovering a critical role of YIPF5 in the human -cell, the authors reported. Our findings highlight a biological pathway essential for -cells.
We are very grateful to the patients, their families, and their doctors for their participation in the study, noted Andrew Hattersley, PhD, one of the senior authors of the study, from the University of Exeter. Without them, we could not have accomplished this. It is our wish that further research will benefit the patients, to facilitate diagnosis and treatment of their diabetes.
Anna Morris, assistant director of research strategy and partnerships at Diabetes UK, which provided funding for the studies, said, These findings provide important new information on how beta cells in the body manufacture insulin and what happens when this process goes wrong. Understanding more about how rarer forms of diabetes develop brings us closer to discovering new ways to cure and prevent all forms of the condition. This is a key part of Diabetes UKs new strategy, and we are proud to have funded De Francos vital research.
- Doctor: COVID-19 cases will continue to slowly go down, but were not out of the woods - Yahoo Money - January 23rd, 2021
- Global Precision Medicine Market With COVID 19 Impact Analysis| Leading Players In-depth Analysis Research Report Foresight to 2027 - KSU | The... - January 23rd, 2021
- Leading Urologist Doubles Down on CaverStem Regenerative Stem Cell Procedure for Treatment of Erectile Dysfunction in Men - PRNewswire - January 22nd, 2021
- Sisters who organised an Ilkley fundraising ball are to be honoured - Wharfedale Observer - January 22nd, 2021
- Medical Doctor: Roes Overlooking of the Consensus of Societal Morality and Science Reverberates to This Day - National Catholic Register - January 22nd, 2021
- DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) Becomes the First FDA-Approved Treatment for Patients with Newly Diagnosed Light Chain (AL)... - January 22nd, 2021
- Seattle researchers find clues for treatments that could eliminate HIV in infected patients - GeekWire - January 14th, 2021
- Flow Cytometry Market is Projected to Reach a Value of US$8100 Mn by the End of 2025 - KSU | The Sentinel Newspaper - January 14th, 2021
- Doctors diagnosed a Suffolk teen with a rare condition. Now, his mom is part of the solution - 13newsnow.com WVEC - January 12th, 2021
- Cassville club assists 2 families as they recover from illness - telegraphherald.com - January 12th, 2021
- The 26 billion-dollar startups to watch that are revolutionizing healthcare in 2021 - Business Insider - January 12th, 2021
- Global Precision Medicine Market 2020 Overview By Size, Share, Trends, Growth Factors and Leading Players With Detailed Analysis of Industry Structure... - January 12th, 2021
- More than 250 articles and a book later, the Valley Doctor bids adieu - San Lorenzo Valley Press-Banner - January 12th, 2021
- Groundbreaking Treatment for Severe COVID-19 Using Stem Cells It's Like Smart Bomb Technology in the Lung - SciTechDaily - January 5th, 2021
- New combo therapy offered against refractory T-cell lymphoma - Korea Biomedical Review - January 5th, 2021
- Hair Growth Treatment Secrets Bollywood Will Never Tell You About - Times of India - January 5th, 2021
- Are metabolic hormones the next frontier in cancer treatment? - MedCity News - January 5th, 2021
- Limerick toddler to wait six months for trial cancer treatment after family raises over 400,000 - Extra.ie - January 5th, 2021
- West Lothian mum fighting for her life after back pain turned out to be terminal blood cancer - Edinburgh Live - January 5th, 2021
- MorphoSys and Incyte Announce the Acceptance of the Swissmedic Marketing Authorization Application for Tafasitamab - Yahoo Finance UK - January 5th, 2021
- A Wish Come True urges plungers to dump a bucket of ice water on themselves for this year's fundraiser - Fall River Herald News - December 26th, 2020
- Ashley Cain says over 80,000 people registered for stem cell donation in 48 hours after appeal to save baby - The Sun - December 22nd, 2020
- The 11 most mind-blowing, awe-inspiring health discoveries and innovations of 2020 - Business Insider - Business Insider - December 22nd, 2020
- 3-year-old patient successfully treated for rare fatal disease- familial Hemophagocytic lymphohistiocytosis (HLH) at Fortis Hospital Shalimar Bagh -... - December 22nd, 2020
- Startups are racing to reproduce breast milk in the lab - MIT Technology Review - December 22nd, 2020
- Hand weakness: Causes, symptoms, treatment, and seeking help - Medical News Today - December 22nd, 2020
- Gujarat Issues Health Advisory On Fungal Infection With "50% Mortality Rate" - NDTV - December 22nd, 2020
- A side-by-side comparison of the Pfizer/BioNTech and Moderna vaccines - STAT - December 22nd, 2020
- City of Hope Doctors Present Innovative Therapies to Better Treat Blood Cancers at American Society of Hematology Virtual Conference - Business Wire - December 9th, 2020
- Medical technologies that will disrupt (and improve) healthcare in the 2020s - Universe.byu.edu - December 9th, 2020
- Community Cord Blood Banking saves life of child with aplastic anaemia - The Hindu - November 20th, 2020
- Arya Lloyd: Father launches global search for blood stem cell donor to save his 12-year-old daughter - Sky News - November 20th, 2020
- Blood Cancer: Science Reveal Five Easily Missed Signs of Leukemia - Science Times - November 20th, 2020
- Karnataka:Community cord blood banking emerges as lifesaver - United News of India - November 18th, 2020
- How CAR-T Cell Therapy is Being Used in the Field of Blood Cancer Treatment - Curetoday.com - November 16th, 2020
- Election results for California Propositions 14, 18, 23, and 24 - FOX 11 Los Angeles - November 16th, 2020
- Cell Separation Beads Market to Witness Robust Expansion Throughout the Forecast Period 2018-2028 - The Daily Philadelphian - November 16th, 2020
- Fight for the rights of unborn - The Daily Telegram - November 11th, 2020
- Doctors Debate: Is Intensive or Low-Intensity Chemotherapy Plus BCR-ABL TKI Therapy Best for Treatment of Ph+ ALL? - Targeted Oncology - November 11th, 2020
- Record number of stem cell donors apply after Ex On The Beach star plea - expressandstar.com - November 11th, 2020
- Bisbee: A commitment to health care initiatives The Journal Record - Journal Record - November 11th, 2020
- California election results: Where state propositions stand as of Thursday at 5 p.m. - Desert Sun - November 11th, 2020
- Critically ill Indonesian woman thanks Taiwan for saving life - Taiwan News - November 7th, 2020
- City of Hope Doctors Present New Research on Bone Marrow Transplants, Immunotherapy and Other Blood Cancer Treatments - Business Wire - November 7th, 2020
- Daily Edition for Wednesday, November 4, 2020 - California Healthline - November 7th, 2020
- 'We're truly blood brothers' - Stanford coach David Shaw and his recent fight to save his brother, Eric - ESPN - November 7th, 2020
- 'We're really blood brothers' - Stanford coach David Shaw and his current battle to save lots of his brother, Eric - The Shepherd of the Hills Gazette - November 7th, 2020
- Mark Drought: Are we on the brink of another civil war? - The Advocate - November 7th, 2020
- What to eat when you have the flu, recommended by doctors - Business Insider India - October 30th, 2020
- Fine-Tuning Treatments for COVID-19 - American Council on Science and Health - October 30th, 2020
- Aborted girl fetus kidneys made Trumps CoV meds. As SARS2 is unfettered in America, this needs thought - Feminine-Perspective Magazine (FPMag) - October 30th, 2020
- What to Know in Washington: Provisional Ballots May Play Role - Bloomberg Government - October 30th, 2020
- Unless the country invests in cancer care, the statistics for breast cancer will be bleak: Dr Anthony Pais, .. - ETHealthworld.com - October 23rd, 2020
- Autologous Fat Grafting Market Scope Analysis 2019 to 2029 - The Think Curiouser - October 23rd, 2020
- How Clinique La Prairie Is Keeping Humanity Fashionably Healthy In The Age Of Covid - Forbes - October 23rd, 2020
- The Anthony Nolan and NHS Stem Cell Registry - The Hippocratic Post - October 21st, 2020
- Jeff Bridges is one of the 85,000-plus lymphoma cases expected in the U.S. this year - MarketWatch - October 21st, 2020
- YOUR HEALTH: Saving an unborn baby breaking apart in the womb - WQAD.com - October 21st, 2020
- Orgenesis completes acquisition of Koligo Therapeutics and announces additional acquisition of Icellator(R) Technology from Tissue Genesis in related... - October 21st, 2020
- SA becomes 2nd country to allow 16 and 17-year-olds to donate bone marrow - News24 - October 21st, 2020
- Stem Cell Therapy Market to Witness Steady Expansion During 2025 KYT24 - KYT24 - October 21st, 2020
- Mohammed Hussain Alqahtani shares his insights about the evolution of plastic surgery - LA Progressive - October 21st, 2020
- Manya Saaraswat Makes Top 5 Finish in 2020 Miss World America Competition, Three Other Indian Americans in Top 10 - India West - October 21st, 2020
- Banking wisdom: Teen saving stem cells in hopes of future treatment - LubbockOnline.com - October 15th, 2020
- Mohammed Hussain Alqahtani Discusses the Future of Plastic Surgery - The Jerusalem Post - October 15th, 2020
- The story of how a biotech co. came to the aid of an ill 9-year-old boy - Stockhouse - October 15th, 2020
- Where Amy Coney Barrett Stands on IVF - Glamour - October 15th, 2020
- Regeneron, Trump, and the alleged hypocrisy of the pro-life movement - Christian Post - October 15th, 2020
- Life Sciences - a year to remember - Lexology - October 15th, 2020
- Proposition 14: With Handful of Cures, Calif. Stem Cell Agency Has Mixed Record. Will Voters Pony Up Another $5.5 Billion? - KQED - October 8th, 2020
- Woman who lost her partner to cancer last year set to run 10K in his memory - Warrington Guardian - October 8th, 2020
- Different Types of Childhood Cancer | INTEGRIS - Integris - October 3rd, 2020
- A perfect match: Bone marrow transplant saves twin brother's life. Now their family pays it forward - 11Alive.com WXIA - October 3rd, 2020
- Baby whose nosebleeds turned out to be deadly condition saved by stranger - Mirror Online - October 3rd, 2020
- Over 40 lakh people in Telangana have developed COVID-19 antibodies: Health Minister Eatala - The New Indian Express - October 3rd, 2020
- Coming of Age: New Research Efforts are Improving Treatment of Childhood Blood Cancers - Curetoday.com - September 23rd, 2020
- World Rose Day 2020: History and significance of the welfare of cancer patients - Hindustan Times - September 23rd, 2020
- Guide to Voting on Propositions and the City of San Bernardino's Measure S - Black Voice News - September 23rd, 2020
- Blood Cancer Awareness Month 2020 - Everyday Health - September 23rd, 2020
- CARLTON FLETCHER: McConnell is the poster boy for sleazy, partisan politics - The Albany Herald - September 23rd, 2020