Restoring Insulin Secretion

Can nonfunctioning beta cells be rejuvenated? Researchers from Florida State University think they can.

In a paper published in PLOS Computational Biology, the researchers, led by Richard Bertram, postulate that it's oscillating pulses of glucose that cause the oscillating pulses of insulin that are seen in healthy people. In nondiabetics, insulin isn't secreted continuously but in pulses, and it's been known for some time that this pulsatile insulin release is lost in people with type 2 diabetes. But no one knew why.

These researchers used sophisticated technology and mathematical modeling to come up with a new model, a Dual Oscillator Model (this type of model has been used in other research, for example, in understanding circadian rhythms here and here). They first put beta cells from mice in a high-glucose environment and found that they lost the pulsatile insulin secretion. Then by using their techniques to manipulate the glucose levels in ways suggested by the mathematical modeling, they were able to resuscitate the beta cells so that they produced insulin again in a healthy pulsatile way.

This technique is nowhere near the stage at which it could be used clinically to cure type 2 diabetes. But it's exciting because it suggests that a type 2 cure is possible, at least in those with viable beta cells. Those cells apparently aren't dead; they're just not functioning properly.

The authors' model is described in detail in their paper, the full text of which is free online. It's fairly dense and mathematical. They found that in response to glucose, some beta cells produce electrically driven fast oscillations in calcium levels, and other produce metabolically driven slow oscillations. They suggest that these two types of cells cooperate to produce pulsatile insulin secretion.

Clearly, creating conditions in vivo that would replicate the results found in their "microfluidic device" would not be simple. But the more we understand about how beta cells operate, the better. And their finding that continuously high glucose levels caused the beta cells to lose their oscillating insulin pulses is another indication that the standard Western lifestyle with too many calories as well as too many carbohydrate foods is not a good idea. Many close relatives of people with type 2 diabetes lack oscillating insulin pulses, suggesting a high risk of progressing to full-blown diabetes.

Maybe this new way of looking things will help us to find at-risk people in the very early stages, when their condition can be truly reversed.