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The Endocrinologist


Issue 141 Autumn 2021

Endocrinologist > Autumn 2021 > Hot topics


Mechanisms of β cell dedifferentiation in diabetes

MARTIN HALUZIK, CO-EDITOR-IN-CHIEF, JOURNAL OF ENDOCRINOLOGY | Hot topics



For this anniversary issue, we invited the Editors-in-Chief of the Society's journals to write about a topic of their choice.

Type 2 diabetes represents one of the most significant challenges globally for healthcare systems, owing to its steadily increasing prevalence and highly expensive treatment. The most important mechanism of type 2 diabetes progression is β cell loss, due to apoptosis and also dedifferentiation. Unlike apoptosis, β cell dedifferentiation is a relatively new concept, first proposed less than ten years ago.

One of the most comprehensive and attractive reviews of this topic was published by Bensellam and colleagues in Journal of Endocrinology. It extensively covers all aspects of this important pathophysiological process, including its mechanism, aspects at the molecular level, and its consequences.

The β cell dedifferentiation is a very complex process, comprising downregulation of insulin gene expression, downregulation of β cell-enriched genes, upregulation of β cell-forbidden genes and activation of stress response genes. Many experimental data describe possible approaches to reverse the process of dedifferentiation and restore functional β cell mass in experimental models of diabetes. Interestingly, however, none of these have been really successful in humans.

One of the interesting approaches suggested in this review could be alleviation of β cell stress, which has proved successful in numerous experimental studies. Furthermore, some studies suggest that recent glucose-lowering therapies, including glucagon-like peptide-1 receptor agonists and sodium glucose co-transporter-2 inhibitors, could also act through modification of β cell dedifferentiation.

This review is definitely worth reading, not only by those interested in experimental research in type 2 diabetes, but also by clinicians, as it gives a very broad and thorough perspective on an important mechanism, which might become a valuable target for future anti-diabetic therapies.

Read the full article in Journal of Endocrinology 236 R109–R143



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