Understanding how insulin producing cells age could help with treatment for type 2 diabetes

by Barbara Hewitt on April 25, 2017

Scientists in the United States have discovered how insulin producing cells show their age in a development that could lead to a better understanding of type 2 diabetes.

The researchers from the Joslin Diabetes Centre in Boston hope that examining the markers of aging will help us understand how beta cells begin to fail in type 2 diabetes.

Experts have puzzled for decades about why insulin producing beta cells in one pancreatic islet often look and behave quite differently than their counterparts in the same islet or in nearby islets.

Using newly identified cellular markers of aging, the scientists have shown that this diversity may be driven at least in part by differently aged beta cell populations within the pancreas.

Additionally, the Joslin team demonstrated that the aging of beta cells, with associated losses of their insulin secretion, can be accelerated by insulin resistance, a condition that can lead toward type 2 diabetes.

‘This research opens up an entirely new set of questions about the development of type 2 diabetes,’ said Susan Bonner-Weir, a Joslin senior investigator who is also professor of medicine at Harvard Medical School.

She explained that type 2 diabetes worsens over time as beta cells die off or perform less effectively for reasons that are not well understood, although scientists have long known that beta cells change significantly over time.

The research involved looking at beta cells in very old mice and they compared them with younger, genetically identical mice and were struck by dramatic difference in the genes expressed by beta cells in animals of various ages.

The researchers followed up to identify markers of aging in these cells, using several mouse models, including one with impaired glucose tolerance, a contributor to type 2 diabetes progression, and another that shows markers of rapid aging.

The scientists identified several markers of aging beta cells, including one protein called IGF1R that is an important player in cell survival. The markers highlighted the striking diversity of beta cell aging, and functional decline, both within and between islets in both mouse and human pancreases.

They believe that the diversity of age among beta cells may be responsible at least in part for the striking heterogeneity that has been observed in both mice and humans. ‘We showed that this heterogeneity may be based on different populations of different aged beta cells,’ said Bonner-Weir.

‘Even in young animals, where many beta cells are still immature, you may have other beta cells that are at the end of their lifespan. Each life stage may have a different phenotype, that is a different gene expression and function, than the other stages,’ she explained. The scientists found that two of the aging markers were significantly increased among people with type 2 diabetes. The researchers also detected surprising numbers of aged beta cells in people as young as 20.

The team will now follow up the research using more human islets and trying to understand how many of these functions translate from animal models to humans and also try to pinpoint factors that boost aging in beta cells, examining whether this aging is reversible and finding potential ways to reduce related metabolic stresses.

The research also may help to suggest answers to some puzzles in type 1 diabetes, including why some cells seem to be more resistant to the autoimmune attack that causes the disease and how beta cells can be found in some people who have had the condition for decades.

The opinions expressed in this article do not necessarily reflect the views of the DiabetesForum.com Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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