New measure of insulin-making cells could gauge diabetes progression, treatment

August 10, 2017 by David Tenenbaum, University of Wisconsin-Madison
Baseline PET scan shows uptake of manganese chloride tracer in mouse pancreas, in research at the University of Wisconsin-Madison department of radiology. Signal is greatly reduced in mice given a drug that inhibits insulin production, and conversely, intensified in mice given a stimulator of insulin production. Credit: Reinier Hernandez et al UW-Madison, Diabetes, August, 2017.

Researchers at the University of Wisconsin-Madison have developed a new measurement for the volume and activity of beta cells, the source of the sugar-regulating hormone insulin.

In a study published in the August edition of the journal Diabetes, Weibo Cai and colleagues used a PET scanner to detect minute levels of a radioactive chemical in the mouse pancreas. Cai, the senior author of the study and an associate professor of radiology, says that unlike previous methods for measuring the quantity of , the also measures how actively these cells are making insulin.

PET scanning, or , is used to detect minute quantities of tracers, commonly for finding cancer and metastases. This area is a specialty of Cai. Cai says the may be used to evaluate treatments or cell transplants intended to slow or reverse diabetes.

With a provisional patent filed through the Wisconsin Alumni Research Foundation, Cai has begun planning a series of human trials that could lead to Food and Drug Administration clearance for a new method to determine the quantity and condition of the beta cells. The first step in these trials would look at the distribution and potential toxicity of the radioactive manganese chloride used as a tracer.

A shortage of insulin, due to the death or inactivity of the beta cells, causes type I (formerly "juvenile") diabetes. The same problem can also cause type II diabetes. But this condition, once called "adult onset" diabetes, can also result from insufficient response to insulin. "In some conditions you can have an adequate number of beta cells, but not all of them are functioning," says Cai. "We measure volume and get a product of function times volume, which is what everybody wants to know."

The chosen tracer has a short half-life, so the exposure to radiation is no greater than what is now used in the many PET scans used to detect cancer.

Because blood sugar tests are cheap and reliable, Cai is not proposing to replace them for detecting diabetes. Instead, the new test could be used to track the effectiveness of medicines and other measures intended to dampen the immune assault that kills beta cells.

The test could offer advantages over earlier methods to detect and analyze beta cells, Cai says. Some magnetic resonance techniques can give information about the quantity and function of beta cells, he says, but they use a dose of manganese chloride that is at least 1 million times higher than the new PET technique, suggesting an advantage in lower toxicity.

Other tests detect beta cells by identifying receptors that are unique to those cells, "but even if cells are not functioning, the receptors are still there," Cai says, "so that does not tell you if they are making insulin. Our test is based on the calcium channel, a portal that the cell uses to exchange chemicals with its environment. The cell has to be active to take up manganese chloride, therefore it's functioning, and if you have more functioning beta cells, then you have more insulin."

Overall, Cai says, "We don't think there is another way to do this with this degree of accuracy."

The other authors included Matthew Merrins and Michelle Kimple, both assistant professors of medicine at UW-Madison who focus on diabetes research.

The development of the new test is more proof that chance favors the prepared mind, says Cai. First author Reinier Hernandez, who was Cai's graduate student and is now a post-doctoral radiology researcher in Madison, came up with the idea when he noticed high uptake of manganese chloride in the pancreas while exploring a PET tracer for cancer. Plenty of people saw apples fall from a tree, but at least according to legend, it was only Isaac Newton who was prompted to think deeply about gravity. "When the apple falls from the tree, you have to put out your hand to catch it," Cai says. "Reinier did. Another person might have missed it."

Preparation played a second crucial role in the story, adds Cai. "People knew that manganese chloride uptakes in the beta , but nobody could make radioisotopes that were pure enough. But Jerry Nickles and Jonathan Engle [the past and present directors of the campus PET Cyclotron Laboratory] are the best in the world at making chemically pure manganese chloride with determined radiological activity. So we were only ones able to pull this off."

Explore further: Insulin release is controlled by the amount of Epac2A at the secretory vesicles

Related Stories

Insulin release is controlled by the amount of Epac2A at the secretory vesicles

July 7, 2017
Specialized beta cells in the pancreas release the hormone insulin to control our blood glucose levels, and failure of this mechanism is central to the development of type-2 diabetes. How much and when insulin is released ...

Scientists study how some insulin-producing cells survive in type 1 diabetes

February 9, 2017
A Yale-led research team identified how insulin-producing cells that are typically destroyed in type 1 diabetes can change in order to survive immune attack. The finding may lead to strategies for recovering these cells in ...

Pathways leading to beta cell division identified, may aid diabetes treatment

May 2, 2017
Pancreatic beta cells help maintain normal blood glucose levels by producing the hormone insulin—the master regulator of energy (glucose). Impairment and the loss of beta cells interrupts insulin production, leading to ...

Team cures diabetes in mice without side effects

May 5, 2017
A potential cure for Type 1 diabetes looms on the horizon in San Antonio, and the novel approach would also allow Type 2 diabetics to stop insulin shots.

Researchers identify new pathway to regenerate insulin-producing cells

September 21, 2015
Researchers at the University of Massachusetts Medical School have discovered a new pathway that triggers regeneration of beta cells in the pancreas, a key development that may aid in the development of diabetes treatments. ...

New type of insulin-producing cell discovered

April 4, 2017
In people with type I diabetes, insulin-producing beta cells in the pancreas die and are not replaced. Without these cells, the body loses the ability to control blood glucose. Researchers at the University of California, ...

Recommended for you

Researchers cure type 2 diabetes and obesity in mice using gene therapy

July 10, 2018
A research team from the UAB led by Professor Fatima Bosch has managed to cure obesity and type 2 diabetes in mice using gene therapy.

Human clinical trial reveals verapamil as an effective type 1 diabetes therapy

July 9, 2018
Researchers at the University of Alabama at Birmingham Comprehensive Diabetes Center have discovered a safe and effective novel therapy to reduce insulin requirements and hypoglycemic episodes in adult subjects with recent ...

New targets found to reduce blood vessel damage in diabetes

July 9, 2018
In diabetes, both the tightly woven endothelial cells that line our blood vessels and the powerhouses that drive those cells start to come apart as early steps in the destruction of our vasculature.

Insurance gaps linked to five-fold rise in hospital stays for adults with type 1 diabetes

July 9, 2018
For a million American adults, living with type 1 diabetes means a constant need for insulin medication, blood sugar testing supplies and specialized care, to keep them healthy and prevent a crisis that could end up in an ...

Abnormal branched-chain amino acid breakdown may raise diabetes risk

July 5, 2018
In the U.S., about five out of 100 expectant mothers develop gestational diabetes mellitus (GDM), a temporary form of diabetes in which hormonal changes disrupt insulin function. Although GDM is often symptomless and subsides ...

Air pollution contributes significantly to diabetes globally

June 30, 2018
New research links outdoor air pollution—even at levels deemed safe—to an increased risk of diabetes globally, according to a study from Washington University School of Medicine in St. Louis and the Veterans Affairs (VA) ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.