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A Factor in Fat Tissue That Helps Preserve Insulin-producing Beta Cells in Mice

Studies of a protein involved in maintaining fat tissue and regulating metabolism have led to new discoveries about β (beta) cell health in mice, with possible implications for treating diabetes. During type 2 diabetes, the body becomes resistant to insulin’s effects and gradually loses insulin-producing β cells in the pancreas. Currently, there are no therapies to stop this loss of functional β cells, leading researchers to study what factors are involved in maintaining β cell health.

Adipsin is a protein secreted by fat cells that was known to increase insulin production in the body in response to glucose (sugar), but its role in diabetes was unclear. Scientists hypothesized that adipsin might be important somehow in maintaining β cell numbers or β cell health. Researchers investigated this possibility by testing a treatment that caused increased adipsin production in a mouse model of type 2 diabetes. They saw improvements over 6 months: blood glucose levels were lower, insulin levels were higher, and fewer β cells had been lost in the mice that were making extra adipsin than in mice that had not received the treatment. Further experiments showed that adipsin’s positive effects on β cell health and function stemmed at least in part from its ability to inhibit production of a protein made in β cells called DUSP26. The researchers found that, in a mouse model of type 2 diabetes, over-production of DUSP26 reduced insulin levels in the blood, whereas reducing DUSP26 levels improved the mice’s blood glucose control. Inhibiting DUSP26 also helped preserve the health of human β cells in the laboratory. Taken together, these results suggested that changes in DUSP26 levels might contribute to development of type 2 diabetes by increasing susceptibility to β cell loss. To explore if the adipsin made by fat cells could potentially protect people from diabetes, scientists studied blood samples and body fat imaging data from a large cohort of men and women. They found that higher adipsin levels in the blood correlated with a lower risk of future diabetes in middle-aged obese adults. The researchers also explored the conundrum that although obesity is a risk factor for type 2 diabetes, adipsin—which is made by fat cells—seems protective. Examining different body fat tissues in people with imaging technology, they found that adipsin in the blood was associated with fat tissue mass under the skin, but not with fat tissue deeper in the body around internal organs (visceral fat) which is linked to metabolic problems.

More research is needed to fully understand the roles adipsin and DUSP26 play in human health and disease, but these new findings suggest that boosting the effects of adipsin or inhibiting those of DUSP26 could be promising targets for future diabetes treatments.

Gómez-Banoy N, Guseh JS, Li G,…Lo JC. Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans. Nat Med 25: 1739-1747, 2019.

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