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Decoding diabetes: Sanford Burnham Prebys lecture discusses advancements for treatment

Pamela Itkin-Ansari, a Sanford Burnham Prebys adjunct associate professor
“We want to make having diabetes invisible to the patient,” says Pamela Itkin-Ansari, a Sanford Burnham Prebys adjunct associate professor.
(Courtesy)

Though COVID-19 has dominated health- and science-related news this year, the Nov. 17 Insights Series webinar by La Jolla’s Sanford Burnham Prebys Medical Discovery Institute focused on work toward understanding diabetes and new ways of treating it.

Diabetes is a chronic disease that occurs when the pancreas is no longer able to make insulin, or when the body cannot make good use of the insulin it produces, according to the International Diabetes Federation.

“Type 1 diabetes can develop at any age but occurs most frequently in children and adolescents,” according to the federation. “When you have Type 1 diabetes, your body produces very little or no insulin, which means that you need daily insulin injections to maintain blood glucose levels under control.”

Type 2, on the other hand, “is more common in adults and accounts for around 90 percent of all diabetes cases.” With Type 2, the body “does not make good use of the insulin that it produces,” according to IDF.

Joe Komsky, senior director of philanthropy at Sanford Burnham Prebys, compared the work the institute is doing to creating an owner’s manual for a car.

“Without an owner’s manual, garages all over the world wouldn’t be able to fix your car,” he said. “But once they have the owner’s manual that talks about how the car works, you can take the car anywhere in the world and, using that manual, a mechanic can fix your car. We’re creating the owner’s manual for human biology.”

Some of the work on diabetes is the first of its kind, he added.

Sanford Burnham Prebys Medical Discovery Institute's Insights Series focuses on different health topics in monthly lectures.
(Courtesy)

Pamela Itkin-Ansari, an SBP adjunct associate professor, talked about the mechanism of diabetes, with a focus on Type 1.

“The pancreas is connected to the gut because 98 percent of the pancreas cells make digestive enzymes. … Only 1 or 2 percent of the pancreas [cells are] the precious eyelets in which the beta cells make insulin,” she said. “Much of the food we eat is converted into the sugar glucose, and that’s the body’s fuel. So when the beta cell senses there is glucose in the bloodstream, it secretes insulin into the bloodstream and insulin acts as the key to unlock every cell so it can take up that glucose to use as fuel. If that insulin is not there, then despite nutrients and glucose, the cells starve.”

About 15 years ago, scientists figured out that they could isolate the eyelets from the pancreas of someone who had died and deliver them to someone who needed them. That way, those with Type 1 diabetes could produce their own insulin.

But, Itkin-Ansari said, the procedure is invasive, can only be done on a few people due to limited resources, and the patient would require lifelong immunosuppression. So her lab started to work toward deriving beta cells from stem cells.

“We were able to produce a virtually unlimited source of beta cells that came from humans,” she said. “That was very exciting. We were able to create a minimally invasive way to introduce these cells in a way that did not require immunosuppression.”

The approach is now in clinical trials at UC San Diego and other research institutions.

“I think this approach is going to revolutionize the life of diabetic patients. We want to make having diabetes invisible to the patient,” she said.

In introducing her colleague, Randal Kaufman, who focused his talk on work being done in the field of Type 2, she said the more common type is “insulin-resistant” diabetes, “so the beta cells keep producing insulin but the cells do not respond to it and the cells are pushed too far and die, and it puts pressure on the remaining ones.”

The source, said Kaufman, director and a professor in SBP’s degenerative-diseases program, is a biological error called “misfolding” that is a “cause of many human diseases.”

Randal Kaufman is director and a professor in SBP's degenerative-diseases program.
(Courtesy)

He said proteins are assembled from amino acids, the creation of which eventually leads to the synthesis of a polypeptide that undergoes folding.

“When it misfolds, the two chains that should not interact become attached and the bond disrupts the folding of molecules … resulting in cell death,” he said. “All my interest in protein folding … has led us to [the discovery] that diabetes is also a problem of proinsulin [the precursor to insulin] folding, and we have been able to accelerate our understanding of the problem with making insulin.”

Kaufman’s team also has identified four proteins that are necessary for proinsulin folding, and, in the past few years, the molecular structure of the bond that results in the misfolding of proinsulin.

“By understanding that structure, we have initiated studies to identify molecules that prevent that interaction,” he said. “We should eventually be able to find a molecule that binds in this pocket and prevents those chains from interacting, therefore promoting effective folding, improving insulin production and improving cell survival. So we get two bangs for one buck.”

The next SBP Insights Series lectures focus on “The Science of Aging” at 1 p.m. Tuesday, Dec. 15, and “How Diet Really Affects Your Body” at 1 p.m. Thursday, Jan. 14. Learn more and view recordings of past lectures at sbpdiscovery.org/sbp-insights. ◆