Good news! Was this one of those serendipitous discoveries?
"Researchers have taken a big step forward in the quest to regenerate the pancreatic beta-cells damaged by type 1 diabetes. Using FDA-approved drugs usually given to patients with rare cancers, they reprogrammed pancreatic cells to produce and secrete insulin in response to glucose. The discovery could mean that, one day, diabetics won't need to take multiple daily insulin injections. ..."
"... Using pancreatic cells derived from a child and adult type 1 diabetic donors, and from a non-diabetic person, a team ... demonstrated how insulin-producing cells that are destroyed in people with type 1 diabetes can be regenerated into glucose sensing and functionally secreting insulin cells. ..."
From the abstract:
"β-cells are a type of endocrine cell found in pancreatic islets that synthesize, store and release insulin. In type 1 diabetes (T1D), T-cells of the immune system selectively destroy the insulin-producing β-cells. Destruction of these cells leads to a lifelong dependence on exogenous insulin administration for survival. Consequently, there is an urgent need to identify novel therapies that stimulate β-cell growth and induce β-cell function. We and others have shown that pancreatic ductal progenitor cells are a promising source for regenerating β-cells for T1D owing to their inherent differentiation capacity. Default transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 methyltransferase. In the present study, we show that transient stimulation of exocrine cells, derived from juvenile and adult T1D donors to the FDA-approved EZH2 inhibitors GSK126 and Tazemetostat (Taz) influence a phenotypic shift towards a β-like cell identity. The transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin modification. Targeting EZH2 is fundamental to β-cell regenerative potential. Reprogrammed pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex vivo. These pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration of β-like cell function."
Closing in on the ultimate quest to regenerate insulin in pancreatic stem cells (Baker Heart and Diabetes Institute)
EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors (open access)
Fig. 1 Inhibition of EZH2 by GSK126 and Tazemetostat reactivates the expression of endocrine markers in exocrine cells
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