If you have diabetes, there is a strong chance you are either on insulin therapy now, or will be in the future. This holds true for people with Type 1 and Type 2 diabetes; both types lead to elevated blood glucose levels.

Insulin therapy maintains blood glucose at healthy levels to prevent the complications that come with diabetes, such as vision problems, kidney disease, neuropathy, heart disease—and the list goes on.

Insulin is usually administered under the skin using a syringe, insulin pen or insulin pump. But scientists are working to change that.

Fred Levine, MD, PhD, a scientist at SBP, has been working on methods to restore pancreatic beta cells—the cells that live in pancreatic islets and store and secrete insulin.

In Type 1 diabetes—an autoimmune disease—beta cells are destroyed by the immune system. In Type 2 diabetes, beta cells gradually lose their ability to produce insulin. “Regenerating insulin-producing beta cells could potentially free millions of patients from daily doses of insulin,” says Levine.

Levine’s initial work, published in two papers in Stem Cells and Cell Death and Disease, began with an observation that injuring the pancreas of diabetic mice causes alpha cells to convert to convert to insulin-producing beta cells. Alpha cells are also located in pancreatic islets but don’t normally produce insulin.

“There was a signal coming from the injured pancreas driving the conversion of alpha cells to beta cells—a process known as transdifferentiation—and we wanted to know what that signal was,” says Levine.

Levine’s next study found that the activation of PAR2, a receptor on alpha cells, was driving the transition to insulin-producing beta cells. That research was published in a later paper Cell Death and Disease.

“This was a good step toward understanding how to restore beta cells, and there are good drug candidates that can activate PAR2, so it could work in humans,” says Levine. “But there was still hurdle. The transdifferentiation process only occurs in the setting of profound beta cell deficiency—there had to be practically zero functional beta cells for alpha cells to convert.”

Most people with Type 2 diabetes and a smaller percentage with Type 1 have some, but not enough, functional beta cells. For these patients, activating PAR2 alone wouldn’t be a sufficient to treat diabetes. Levine’s group hypothesized that there must be an inhibitory signal coming from beta cells preventing the process.

In the latest study, published in Islets, Levine’s research team found that insulin is the inhibitory signal that prevents transdifferentiation.

“It makes sense that insulin inhibits transdifferentiation, because why would your body generate beta cells if you already had a significant number of cells producing insulin,” says Levine. “But biology isn’t perfect, hence the need for insulin therapy.”

“We were able to work around these obstacles and generate insulin-producing beta cells by using a combination of drugs, one that activates PAR2 (2fLI), and two that inhibit insulin secretion and action (diazoxide and S961). It’s a two element process—one which is positively acting on alpha cells and the other repressive of beta cells,” explains Levine.

“Our research offers the prospect of a straightforward pharmacological approach to regenerate insulin-producing cells to treat diabetes,” says Levine. “For Type 2 diabetes, we could potentially drive transdifferentiation in vivo by activating PAR2 and inhibiting insulin for a short term. It could result in restoration of long-term beta cell function.

“For Type 1 diabetes, we would still need to address the autoimmune aspect of the disorder, because new beta cells would continue to be attacked by the immune system,” adds Levine. “But as our understanding and ability to rein in the autoimmune system improves, the approach could be a much needed breakthrough for the disease.”

Susan Davis, U.S. Representative for California’s 53^rd congressional district (D-San Diego), visited our Institute in April and met with several members of the faculty and SBP President Kristiina Vuori, MD, PhD  Davis, a strong advocate for increasing the NIH budget to advance scientific discoveries, has a long history of supporting initiatives on diabetes and cardiovascular health.

Davis was following up on an invitation for a tour of our campus from Chris Larson, PhD, vice president, drug discovery at SBP. Larson sits on the Board of Directors for the Southern California Chapter of the American Diabetes Association and meets regularly with Davis regarding issues related to diabetes care and research.

Pamela Itkin-Ansari, PhD, adjunct professor at SBP met with Davis and shared her research on implanting small encapsulation devices that contain pancreatic islet cells as an approach to treat type 1 (juvenile) diabetes. The work has now progressed to international clinical trials, which impressed Rep. Davis.

As a teenager, Davis worked as a counselor at a camp for diabetic children—most of whom have type 1 diabetes.  The experience led to a lifelong interest in improving the health and welfare of diabetic patients, both type 1 and type 2.

“Congresswoman Davis’ visit went really well,” says Larson, who organized a tour of the Prebys Center, showcasing the high-throughput drug discovery capabilities of the facility. “She was especially keen to learn how our automated technology can screen hundreds of thousands of chemical compounds to find future drugs.

“It was an honor to host Congresswoman Davis, and she and her staff are most welcome to visit anytime,” says Larson.

He doesn’t need money to produce an album. He’s not raising funds to start a new business in his hometown. And he’s not asking for cash because he’s a famous rapper who suddenly finds himself “bankrupt.” He is a young scientist who needs money to conduct research aimed to save lives, so he is turning to crowdfunding.

Joseph Lancman, PhD, is a scientist in the organogenesis lab of Duc Dong, PhD, at Sanford Burnham Prebys Medical Discovery Institute (SBP) in La Jolla. Lancman’s crowdfunding site just went live on Diabetes Research Connection (DRC), a San Diego-based company that created a platform to connect donors directly with early-career scientists. In the next 90 days, Lancman hopes to generate $50,000 for his research project that may provide the scientific breakthrough needed to find a cure for type 1 diabetes. Watch his video here.

“We recently discovered a way to reprogram cells and change their identity without removing them from the body,” Lancman said. “We believe this breakthrough will have great implications for people with degenerative diseases, like diabetes.”

As many as three million Americans have type 1 diabetes.  Millions of children and adults struggle with this disease, yet funding has decreased dramatically for research. In fact, the head of the National Institutes of Health (NIH)  said last year that young scientists in this country now face the worst funding in 50 years.

So, if you are a young scientist with a great idea, where do you go? Alberto Hayek, MD, co-founder and president of the DRC and world-renowned diabetes expert, says some go away. “Due to the limited funding available, scientists just starting out in their career are forced to leave the field of diabetes and go to fields that have more funding. We are giving scientists the funding needed to test and validate research that departs from conventional thinking,” Hayek said.

Dong says his lab heard about DRC from others in the field. “The DRC is committed to funding innovative projects that may not be considered mainstream approaches. The crowdfunding model itself is highly innovative, by making sure that 100% of donations will go directly into specific labs and projects chosen by the individual donors,” Dong said.

And it works. Since DRC launched its platform in 2014, six research projects from all over the country have been 100% funded. Every dollar of the money raised goes directly to the scientist. The power to fund projects has been given to the people.

Lancman has a total of 90 days to make it happen. He needs 5,000 people to donate $10 each in order to reach his goal. He’s excited to be able to continue to work towards a cure for diabetes, and allow people to live full lives without painful daily insulin injections.

Come on, social media.