Nav: Home

Research shows nerve growth protein controls blood sugar

November 14, 2016

Research led by a Johns Hopkins University biologist demonstrates the workings of a biochemical pathway that helps control glucose in the bloodstream, a development that could potentially lead to treatments for diabetes.

In a paper published in the current issue of Developmental Cell, Jessica Houtz, a graduate student working with Rejji Kuruvilla in the Department of Biology at Johns Hopkins, shows that a protein that regulates the development of nerve cells also plays a role in prompting cells in the pancreas to release insulin, a hormone that helps to maintain a normal level of blood sugar.

Kuruvilla worked on the project with Johns Hopkins colleagues Houtz, who is the lead author, and Philip Borden and Alexis Ceasrine, also doctoral students in the Biology Department. Also taking part was Liliana Minichiello of the Department of Pharmacology at the University of Oxford.

The research is potentially relevant to type-2 diabetes, the most common form of the disease, affecting nearly one in 10 Americans. With this form of the condition, which can appear at any time of life, the body makes insulin, but is either not releasing enough of it or not using the regulatory chemical efficiently to control blood sugar. In type-1 diabetes, which appears in childhood, an immune response gone awry destroys the body's ability to produce insulin altogether.

The research on insulin represents a detour for Kuruvilla, whose work has focused on development of the peripheral nervous system. She has studied a group of proteins called neurotrophins, and in particular nerve growth factor [NGF]. These proteins nurture the growth of neurons, the cells of the nervous system.

It has been known for some time that neurons and the pancreatic beta cells, or β-cells, that reside in clusters called islets of Langerhans and produce insulin, have many similarities in molecular makeup and signaling receptors. Receptors are proteins on cell surfaces that respond to particular chemicals and have critical roles in biochemical pathways. Both neurons and pancreatic β-cells have the receptors for neurotrophins.

"This project was sparked by seeing NGF receptors present in beta-cells," Kuruvilla said. The question was, she said: "What are these receptors doing outside the nervous system?"

It turns out that NGF performs a function in the mature pancreas that has nothing to do with supporting neurons. Specifically, the research team traced a chain of biochemical signals showing that elevated blood glucose causes NGF to be released from blood vessels in the pancreas, and that the NGF signal then prompts pancreatic β-cells to relax their rigid cytoskeletal structure, releasing insulin granules into the blood stream. Although β-cells also make NGF, Kuruvilla and her team found that it was the NGF released from the blood vessels that is needed for insulin secretion.

Using genetic manipulation in mice and drugs to block NGF signaling in β-cells, they were able to disrupt distinct elements of this signaling sequence, to show that this classical neuronal pathway is necessary to enhance insulin secretion and glucose tolerance in mice. Importantly, Kuruvilla and colleagues found that NGF's ability to enhance insulin secretion in response to high glucose also occurs in human β-cells.

It is not yet clear how this system is affected in people with diabetes. "We are very interested in knowing whether aspects of this pathway are disrupted in pre-diabetic individuals," Kuruvilla said. It would be of interest to determine if NGF or small molecules that bind and activate NGF receptors in the pancreas could be of potential use in the treatment of type-2 diabetes. These are questions to be pursued in further research.
-end-
This research was supported by National Institutes of Health grant (R01DK108267) to Kuruvilla and an NIH training grant (T32GM007231) to Houtz, Borden and Ceasrine.

Johns Hopkins University

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.