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There are already a number of promising research approaches in regenerative diabetes research, all of which aim to preserve beta cell mass and function or to renew destroyed beta cells. If it were possible to convert progenitor cells and other cells of the pancreas into insulin-producing beta cells in humans, the insulin secretion could be normalized and thereby treat diabetes causally. A long-term goal would even be to prevent the onset of type 1 diabetes – even if it was possible to prevent the destruction of beta cells in genetically prejudiced people from the outset.

The regeneration of beta cells is the focus of many activities in diabetes research. The aim is to stop the disease early and prevent dangerous secondary diseases.

To date, too little is known about the molecular mechanisms that regulate or control the maintenance, renewal, and differentiation of insulin-producing beta cells in the pancreas.

But in Germany alone, there are several research centers that are intensively involved in regenerative research approaches in diabetes and prediabetes. These research projects are funded by, among others, the German Center for Diabetes Research.

How do beta cells renew themselves?

It is not yet known in detail how the beta cell mass regulates at all, whether by conversion from other cells, by new formation or by cell division from the stock, and what significance the different processes have. Scientists speculate, however, that depending on the disease, various regeneration mechanisms, possibly also side by side, expire.

For example, it has already been shown that new beta cells form from pancreatic duct cells or glandular cells located outside the islands. Once you understand the exact factors for this transformation, new treatments can be developed.

Alpha becomes beta

When beta-cell function is lost and dwindling insulin does not inhibit alpha cell glucagon secretion, the level of the hormone glucagon (hyperglucagonemia) increases and blood sugar levels increase as the disease progresses. Interestingly enough, scientists in the model system were able to prove that beta cells can also be produced from the pancreatic alpha cells. Several research groups are now working to identify the appropriate molecular and genetic mechanisms to actively control this transformation process.

The different cell types regulate each other. Therefore, scientists are pursuing the approach of producing groups of alpha-beta and other cells from stem cells and transplanting these cell communities. The mutual regulation of the opponents limits the risk of hypoglycaemia or hyperinsulinemia.

How can a dismantling of beta cells be stopped?

Scientists are also going to the hypothesis that beta cells when, as in the early stages of type 2 diabetes, come under inflammatory stress may reverse. These so-called dedifferentiated progenitor cell-like cells could protect themselves from inflammatory stress and form the basis for re-differentiation into beta cells. Certainly, however, the glucose-dependent insulin secretion in these dedifferentiated beta cells is disturbed.

A possible approach of beta cell regeneration is thus to differentiate such dedifferentiated beta cells into mature and functional beta cells. In the animal model it has already been shown that this is possible through insulin therapy and lowering the blood sugar level.

Further evidence that beta cells can regenerate is found in obesity surgery: in severely overweight insulin-requiring patients, regeneration of the beta cells occurred shortly after the stomach was surgically reduced and the patients were able to do without insulin administration – and that already before they reduced their weight. Insights into the body’s mechanisms of beta cell regeneration after gastric downsizing may provide future therapeutic approaches.

Overall, however, one knows too little about the mutability of the cells in the pancreas, and places high hopes that put in this field of research manifold possibilities for future therapeutic application.


Stop age-related beta cell loss

Researchers at the Stanford University School of Medicine have succeeded in finding a molecular key pathway responsible for slowing beta cell growth with age. The scientists hope to someday be able to control this signaling pathway in humans in such a way that beta cell function is maintained despite the aging process.

An important role is played by the growth factor PDGF, which decreases in both mice and humans over time. If the PDGF receptor signaling pathway is artificially activated, the number of beta cells in the pancreas increases without causing hypoglycaemia.