New Discovery Could Pave The Way For Improved Treatments For Diabetes (Biology)

Monash University researchers have uncovered the barrier to β-cell (beta cell) regeneration that could pave the way for improved treatments for diabetes and diseases that involve organ and tissue damage.

The human body doesn’t repair itself very well, with our liver the only organ that can regenerate efficiently. We have limited capacity to regenerate new cells or tissue after birth as the genes involved in development are switched off.

This process happens through DNA methylation, a biological process where chemicals (methyl groups) are written on DNA and modify the way the gene functions. This modification effectively silences genes of progenitor cells (early descendants of stem cells) in the body and thereby the ability for the pancreas to generate the insulin producing β-cells.

Using mouse models, the study published in Regenerative Medicine, led by Professor Sam El-Osta from Monash Central Clinical School, found that the DNA methylation content of two key developmental genes Ngn3 and Sox 11 were diminished, effectively making them ‘repair’ dormant.

However, through demethylation, progenitor cells can be reawakened, restoring their capacity to become new insulin producing beta cells paving the way towards improved treatments for Type 1 and Type 2 diabetes.

“The collaboration between Dr Keith Al-Hasani and Dr Ishant Khurana has unveiled some surprising results. Their discovery that DNA methylation is a barrier to adult beta-cell regeneration will assist scientists to restore beta-cell function in the pancreas,” said Professor El-Osta.

Currently, replacing the damaged β-cell mass in diabetic patients consists of whole pancreas or islets transplantation. Although efficient, these therapies face the shortage of organ donors together with the associated side effects of immunosuppressive drugs.

Current research focuses on the replacement of the lost β-cells in diabetic patients using several approaches and cell sources. However, critical to exploiting the potential of these regenerative approaches, is understanding how tissue and cellular processes are controlled during development.

Co-first author on the study, Dr Keith Al-Hasani added: “This is a novel and significant finding that will allow us to use these “sleeping beauties” (stem cells like cells) to wake up and become insulin cells to cure diabetes.”

Featured image: Proposed schematic model of DNA methylation as an epigenetic barrier for islet transition and reprogramming in the pancreas. a Pax4 overexpression in adult α-cells (orange) induce their trans-differentiation and conversion into β-like cells (blue). This leads to a shortage in glucagon, which is responsible for the mobilisation of ductal precursor cells (green), these re-expressing the pro-endocrine gene Ngn3 (green), prior to undergoing an EMT and concomitant differentiation into endocrine cells. Such a continuous cycle of conversion/regeneration results in insulin+ cell hyperplasia. b Methylation writing (DNMT’s) and erasing (Tet’s) enzymes are implicated in the regulation of Arx and Pax4, respectively. c Re-expression of Ngn3 is inversely associated with loss of DNA methylation in the ArxKO knockout and Pax4 misexpression animal models. This model of DNA demethylation-mediated reprogramming or dmrE closely corresponds with Tet expression and the loss of gene methylation content and enhanced activity of the mesenchymal marker Sox11. © Khurana et al.

Reference: Khurana, I., Al-Hasani, K., Maxwell, S. et al. DNA methylation status correlates with adult β-cell regeneration capacity. npj Regen Med 6, 7 (2021).

Provided by Monash University

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s