Experimental remedy seems to subdue kind 1 diabetes in laboratory mice

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Experimental treatment can essentially reverse type 1 diabetes in certain types of laboratory mice, according to a number of studies conducted by scientists at the University of Utah Health. Injection of the therapeutic turns cells that normally control glucose production into cells that make insulin.

The researchers say that giving a single dose of a human antibody that suppresses the effects of glucagon, a hormone involved in glucose regulation, triggered a remarkable transformation in the pancreas that resulted in an almost 7-fold increase in insulin cell mass and suppression of diabetic symptoms.

“These animals no longer need insulin injections to never again need treatment for diabetes. They maintain normal blood sugar long after treatment is stopped,” said William L. Holland, Ph.D., co-author on the study and U of U Health Assistant Professor for Nutrition and Integrative Physiology. “For millions of people with type 1 diabetes, this means that we can potentially regenerate their own insulin production capacity, restore their blood sugar levels to normal and, hopefully, help them make progress towards disease freedom.”

However, the researchers warn that they are still a long way from achieving this goal. “This research is certainly promising, but it is probably only the first step of many before we can determine whether this approach works in people with type 1 diabetes,” says Holland. “We have a long, long way to go.”

The study appears in Proceedings of the National Academy of Sciences (PNAS). In addition to U of U Health, researchers from Vanderbilt University Medical Center, Baylor College of Medicine, Lilly Research Laboratories, the University of Texas Southwestern Medical Center, the Dallas Veterans Administration, and the Juvenile Diabetes Research Foundation (JDRF) have contributed to this effort .

Glucagon and insulin are made by groups of cells in the pancreas known as islets of Langerhans. These hormones work together to keep blood sugar under control. However, type 1 diabetes disrupts this process by causing the body’s immune system to attack and destroy insulin-producing cells. As a result, most people with type 1 diabetes rely on insulin injections or pumps to survive.

“By the time people are diagnosed with type 1 diabetes, they will likely have lost 90% of the cells that produce insulin in their bodies,” says E. Danielle Dean, Ph.D., co-author and assistant professor of the study of medicine at Vanderbilt University Medical Center. “In order for a person to achieve glucose control without treating himself or herself with insulin, one has to convince the cells in the body that make insulin to increase their numbers.”

To see if this could happen, Holland, Dean, and colleagues induced diabetes in mice and triggered the death of insulin-producing beta cells in the pancreas. When the same mice were given a human monoclonal antibody called Ab-4, which blocks glucagon binding in the liver, their blood sugar levels normalized and circulating insulin levels were restored.

The researchers dug deeper and tracked glucagon-producing alpha cells with a fluorescent protein marker that glows red. The increased number of glowing red blood cells also produced insulin, suggesting that these glucagon-producing cells had made insulin instead. These first studies were conducted in mice that were able to regenerate insulin-producing cells without disturbing the immune system.

Next, the scientists turned to non-obese diabetic mice (NOD). These animals develop diabetes spontaneously because their overly aggressive immune systems can easily cause beta (insulin) cell death. This condition is very similar to type 1 diabetes in humans. However, treatment with Ab-4 restored insulin production and the regeneration of large numbers of insulin-producing cells in the pancreas.

“It is a very fascinating finding that our treatment protects and restores insulin-producing beta cells even when the immune response is sustained,” says Holland. “It seems that the immune cells can no longer kill the new beta cells.”

However, many potential therapies that increase beta cell mass in mice do not have the same effect on human islets or in patients. To see if they could overcome that, the researchers transplanted human islets into immunodeficient, diabetic mice. They then selectively killed mouse beta (insulin) cells, leaving only the human islets in place. Treatment of these mice with Ab-4 improved glucose control and increased the amount of circulating human insulin in their bloodstream, confirming a benefit to the human islets

These effects were still detectable 40 days after treatment.

In the future, researchers will begin to investigate how alpha cells (glucagon cells) convert into insulin-producing cells and avoid damage by the immune system.

Type 2 diabetes: Too much glucagon when α cells become insulin resistant

More information:
May-Yun Wang et al., “Glucagon Blockade Restores Functional β-Cell Mass in Type 1 Diabetic Mice and Improves Human Islet Function”, PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2022142118 Provided by the University of Utah Health Sciences

Quote: The experimental treatment appears to suppress type 1 diabetes in laboratory mice (2021, February 22), released on February 22, 2021 from https://medicalxpress.com/news/2021-02-experimental-treatment-subdue-diabetes -laboratory.html

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