Can Adult Pancreatic β Cells Regenerate?

Traditional knowledge tells us that it is very difficult for pancreatic β cells to regenerate. Due to the slow dissemination of new scientific knowledge, most people, including many medical professionals, are unaware that our pancreatic β cells continue to proliferate throughout our lifetime (1,2).

Setting aside the recent popular topic of pancreatic stem cell transplants, our bodies naturally possess several mechanisms for pancreatic β cell regeneration. The first mechanism is the most basic: cell division, where one cell divides into two. Research has shown that as long as there are still living β cells in our bodies, regardless of our age, new β cells will be generated through cell division. Cell division is a well-known mechanism, so we won't elaborate further here.

The next mechanism is less familiar. It is generally believed that glucose in the blood damages β cells because high blood sugar can cause these cells to die from overwork. However, new research reports indicate that glucose in the blood can also stimulate the proliferation of new β cells, and this happens in more than one way.

The first method is based on a simple supply-and-demand concept. When glucose levels in the blood are slightly elevated, the body utilizes the isoformation of glucokinase or the interaction between insulin and insulin receptors to stimulate the production of new β cells, thereby improving the ability of insulin production (3).

The second method involves endoplasmic reticulum stress triggered within β cells when blood glucose levels are slightly elevated (note: slightly elevated, not excessively high). This physiological stress signals the body’s insufficient insulin supply, which in turn stimulates the replication of β cells (4).

 In fact, beyond the ability of pancreatic β cells to self-replicate and proliferate, other types of cells in the body can also transform into β cells under the influence of certain regulatory molecules, supplementing the body’s capacity to produce insulin. For example, under the action of certain growth factors, pancreatic alpha cells, delta cells, and exocrine cells can transform into β cells when needed (2).

 Even more interestingly, it’s not just cells within the pancreas that can undergo this transformation. Liver cells and gastrointestinal cells can also convert into β cells under endocrine stimulation, enhancing the body’s ability to produce insulin (2).

Given these numerous mechanisms for β cell proliferation in the body, why did people in the past believe that pancreatic cells couldn’t regenerate? This misconception stems from a broader perspective. In most cases, what we observe is a steady decline in insulin production (resulting from a decrease in the number of β cells), which contributes to the progressive worsening of diabetes.

In reality, the total number of β cells is dynamic. Based on the principle of homeostasis, when the proliferation rate exceeds the cell death rate, the total number of β cells increases over time. Conversely, when the rate of cell death surpasses the rate of proliferation, the β cell mass decreases.

Due to genetic and lifestyle factors, the β cell mass in most people with diabetes remains in a state where cell death outpaces proliferation, leading to disease progression over time. Since β cells continue to replicate and proliferate throughout life, reducing the rate of β cell death (or preserving) becomes a crucial goal in the treatment of diabetes (5).

1. Dor, Y., Brown, J., Martinez, O. et al.Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429, 41–46 (2004).
2. Bourgeois S, Coenen S, Degroote L, Willems L, Van Mulders A, Pierreux J, Heremans Y, De Leu N, Staels W. Harnessing β cell regeneration biology for diabetes therapy. Trends Endocrinol Metab. 2024 Nov;35(11):951-966.
3. Shirakawa J, Terauchi Y. Newer perspective on the coupling between glucose-mediated signaling and β-cell functionality. Endocr J. 2020 Jan 28;67(1):1-8.
4. Sharma RB, O'Donnell AC, Stamateris RE, Ha B, McCloskey KM, Reynolds PR, Arvan P, Alonso LC. Insulin demand regulates β cell number via the unfolded protein response. J Clin Invest. 2015 Oct 1;125(10):3831-46.
5. Sayyed Kassem L, Rajpal A, Barreiro MV, Ismail-Beigi F. Β-cell function in type 2 diabetes (T2DM): Can it be preserved or enhanced? J Diabetes. 2023 Oct;15(10):817-837.