Helping Beta Cells

Two recent research reports concern helping beta cells produce more insulin. Interestingly, they both involve inhibiting something rather than trying to stimulate the beta cells, as the sulfonylurea drugs do.

People think of type 2 diabetes as being caused by insulin resistance and some wonder why you would want to produce more insulin if you have type 2. But in fact, type 2 is often caused by insulin deficiency. That is, you're producing insulin, often more than normal, but it's not enough to overcome your insulin resistance. So more insulin can help.

The first study involves deleting senescent, or old, beta cells from the pancreas. When the Joslin Diabetes Center researchers did this in mice, they found that the remaining beta cells were rejuvenated and started producing enough insulin to keep blood glucose (BG) levels in the normal range.

How did they do this? One approach was genetic modification, which is fine in mice but unlikely to be practical in humans. The other approach was with senolytic drugs, drugs that remove senescent cells. Although you can buy drugs claiming to be senolytics from companies that market supplements, this field is relatively new and large-scale controlled trials have not yet been done. Pilot studies show promise.

The authors of this paper think that diabetes is caused by stress: in type 2 the stress of insulin resistance and in type 1 the stress of an autoimmune attack. Of course this doesn't explain what causes insulin resistance or an autoimmune attack, and these are the underlying problems.

The second study involved removing two signaling molecules that dampen the insulin response. This is the opposite of most approaches, which try to stimulate the insulin response directly instead of inhibiting  inhibitors. The sulfonylureas stimulate insulin release, even when a person is not eating carbohydrate, which means your blood glucose can go low when you're not eating.

These studies were done in mice, and oddly, removing the inhibitors worked only when the mice were on a high-fat diet. The reason for this is not yet known.

The inhibitors are TLR2 and TLR4. TLR stands for toll-like receptor, and normally, TLR2 and TLR4 stimulate the immune system when they detect invadors. But they also work together to block beta cell proliferation, so when you remove them, the beta cells multiply like mad, so much that they can be seen with the naked eye.

There are in fact drugs that inhibit TLR2 and TLR4, but inhibiting them would not only stimulate beta cell growth, but it would inhibit the immune system and make a person susceptible to infection.

Nevertheless these new approaches are interesting and may result in methods to rejuvenate beta cells in people with both types of diabetes (most people with type 1 do have a few beta cells remaining despite the autoimmune attack). How wonderful that would be.



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