Nav: Home

New members found in a transcription factor complex that maintains beta cells

September 04, 2019

BIRMINGHAM, Ala. - Beta cells in pancreatic islets produce insulin to exquisitely regulate blood glucose levels and, thus, provide energy to cells throughout the body. Loss or dysfunction of the beta cells results in diabetes, a major public health threat that can lead to heart disease, neuropathy, blindness and kidney failure.

The future points to several possible therapies for diabetes -- including transplantation of functional beta cells grown in culture into patients, or finding strategies to promote regeneration of a patient's own beta cells. Either of those potential therapies requires basic knowledge of the complex genetic programs that produce and maintain functional beta cells.

Chad Hunter, Ph.D., associate professor in the University of Alabama at Birmingham Comprehensive Diabetes Center and Department of Medicine's Division of Endocrinology, Diabetes and Metabolism, has added a key piece to that basic research in a study published online ahead of print in the Journal of Biological Chemistry.

Hunter studies a protein complex in the nucleus of beta cells that functions something like a molecular Swiss Army knife -- different proteins in the complex have different functions, and yet they work together to regulate genes important for the development and maintenance of functional beta cells. The key protein in the complex is the Islet-1 transcription factor, and Hunter, in a series of previous discoveries, has tracked down other proteins that join with Islet-1 to form the complex.

This complex, in addition to the so-far known protein members, now has been shown to also associate with enzymes RNF20 and RNF40, which are two related ubiquitin ligases. The researchers showed that these RNF enzymes are also key proteins in the complex because disruption of either RNF20 or RNF40 reduced insulin release from cultured beta cells.

"The RNF enzymes can act as transcriptional co-regulators," Hunter said. "They can help change how tightly DNA is wrapped around histone proteins, which is important for packaging genomic DNA within a cell's nucleus. You need to loosen the histone association with the DNA to make the gene accessible, so it can be expressed."

Hunter and colleagues reported that the RNF enzymes and Islet-1 are required for the appearance of the ubiquitin modification on histone 2B proteins in beta cells, which is involved in gene transcription and aids with loosening of the DNA at particular genetic sites.

"This histone modification and RNF proteins are associated with gene expression in multiple cell types, but this is the first time they have been studied in beta cells," Hunter said. "The more we know about how beta cells develop and maintain function, the closer we can come to freeing patients from insulin injections or pharmacological intervention."
-end-
Along with senior author Hunter, Alexa Wade is the first author of the Journal of Biological Chemistry paper, "LIM-domain transcription complexes interact with ring-finger ubiquitin ligases and thereby impact islet β-cell function." Wade is a former UAB undergraduate in the UAB Honors College Science and Technology Honors Program, and earned a Minority Undergraduate Internship award from the American Diabetes Association to perform these studies. She now is a graduate student at Johns Hopkins University.

Co-authors are Yanping Liu, Maigen M. Bethea and Eliana Toren, Division of Endocrinology, Diabetes and Metabolism, UAB Department of Medicine; and Hubert M. Tse, UAB Department of Microbiology.

Support came from National Institutes of Health grants DK111483, DK111181 and GM008111; and American Diabetes Association grants 1-16-JDF-044 and 1-17-MUI-004.

Hunter's study of pancreatic islet developmental biology is part of the basic research arm of the UAB Comprehensive Diabetes Center. The other arms of the center are clinical research and translational research.

University of Alabama at Birmingham

Related Diabetes Articles:

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.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
More Diabetes News and Diabetes Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.