Episodic β-cell death and dedifferentiation during diet-induced obesity and dysglycemia in male mice

What is it about?

Obesity is a risk factor for diabetes, and a national and international focus has been placed on reducing or reversing obesity and its ravages. The inability of β cells in the pancreas to produce sufficient insulin increases the risk of an obese person developing diabetes. It has remained unclear whether this inability to produce sufficient insulin is caused by dying β cells or by β cells that lose their identity, and thereby simply stop producing insulin. The goal of our study was to monitor mice to determine if β-cell death or loss of β-cell identity are features of pre-diabetes. We fed mice a diet high in fat and compared these mice to mice low fat diet. High fat diet-fed mice developed obesity and showed increases in blood sugar, similar to humans. We used a simple blood test to monitor β-cell death in these mice and, at different time points, we analyzed the pancreas of these mice to assess β-cell identity. Our findings showed that β-cell death occurs episodically during early obesity, whereas later in the course of disease many of the remaining β cells begin to lose their identity. Therefore, our study suggests that both the death of β cells and loss of their identity occur during obesity, with death occurring early and loss of identity occurring later. Our studies suggest the need to perform related studies in humans to determine if drugs that might halt β-cell death or loss of β-cell identity might be beneficial in preventing diabetes.

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