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Discovery of a Suspect Enzyme in Humans Could Lead to Powerful Type 1 Therapy

An enzyme that destroys pancreatic beta cells in lab mice has now been observed in human beta cells. Because scientists already know how to delete the mouse gene that produces the enzyme, they are hopeful that the same therapy can eventually be applied to people with type 1 diabetes. If so, it would be one of the most powerful therapies yet for addressing the destruction of insulin-producing beta cells that causes type 1.

Researchers at Eastern Virginia Medical School’s Strelitz Diabetes Center knew that the enzyme, 12-lipoxygenase (12-LO), produces lipids that cause inflammation, killing pancreatic beta cells in lab animals. They suspected that the same enzyme might also be responsible for beta cell death in humans. Thanks to people who donated their bodies to science through the Juvenile Diabetes Research Foundation Islet Resource Center Consortium, the Virginia researchers were able to confirm their suspicion-12-LO is present in human islets of Langerhans, which contain the insulin-producing cells. In some individuals, certain lipids produced by 12-LO inflame beta cells, leading to their death and an associated decline in insulin production that can range from drastic to total.

Now that researchers have confirmed the existence of 12-LO in humans, they can build on the insights gained in their studies of lab animals. In those studies, they figured out a way to “switch off” the gene that produces 12-LO. Once the enzyme was blocked, the damage to beta cells ceased. If they can find a way to block 12-LO in humans, while combining it with therapies designed to restore beta cells, they will have be in position to create a powerful new therapy for type 1.

The study was headed by Jerry Nadler, MD, chair of internal medicine and director of the Strelitz Diabetes Center. His team’s findings were published in the February issue of The Journal of Clinical Endocrinology and Metabolism.

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New study finds possible source of beta cell destruction that leads to type 1 diabetes

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