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Unexpected outcome (positive or negative) including adverse drug reactions
Case report
Azacitidine-induced hyperglycaemia
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  • Published on: 20 March 2021
    Aza induced hyperglycemia

    The author proposes two possible mechanisms for Aza induced hyperglycemia 1. Impaired beta cell function in pancreas via epigenetic mechanism 2. Increased secretion of cortisol. I suggest another possibility. A recent paper by Strand et al reports that Aza, a DNMT1 inhibitor, is a potent inducer of PTEN (this work done in vascular smooth muscle cells). It is well known that PTEN is an inhibitor of downstream elements of the insulin pathway, specifically PI3K-AKT-mTOR pathway and this results in insulin resistance. I suggest that the hyperglycemic activity of Aza is by PTEN induction of insulin resistance.
    Strand KA, Lu S, Mutryn MF, et al. High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN. Arterioscler Thromb Vasc Biol. 2020;40:1854–1869.

    Conflict of Interest:
    None declared.