ArticleDiabetologia2026
Harmine selectively enhances human beta cell identity markers and function via protein kinase A pathways.
Article in Diabetologia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
- Update of
Authors and funding
17 authors.
Funding
Abstract
aims/hypothesisHarmine and other small-molecule inhibitors of the kinase, dual tyrosine-regulated kinase 1A (DYRK1A), induce human beta cells to replicate and regenerate in vitro and in vivo and are effective at reversing diabetes in animal models. In addition to its beta cell proliferative and regenerative effects, which result from inhibition of DYRK1A ('Target 1'), harmine also induces expression of essential transcription factors and other genes involved in beta cell identity and function, exemplified by PDX1, MAFA, NKX6.1, MAFB, SIX3, SLC2A2, ENTPD3 and others. Harmine also rapidly enhances glucose-stimulated insulin secretion in vitro and in vivo. These beta cell identity-enhancing effects are not due to DYRK1A inhibition. We hypothesise that they reflect interactions of harmine with a second target ('Target 2'). We aimed to identify Target 2.
methodsWe performed an in-depth analysis of multiple different small-molecule inhibitors of DYRK1A in human pancreatic islets using gene expression, single-cell RNA-seq, proliferation, immunocytochemistry of beta cell transcription factors and identity markers, and solid-phase precipitation combined with proteomics.
resultsAll small-molecule DYRK1A inhibitors studied (harmine, 2-2c, 5-IT, INDY, leucettine, CC-401, GNF4877) induced human beta cell proliferation via inhibition of DYRK1A. In contrast, silencing DYRK1A had no effect on beta cell transcription factors and identity markers. Further, harmine, 2-2c and 5-IT but not INDY, leucettine, CC-401 or GNF4877 enhanced expression of beta cell phenotypic markers. The enhanced expression of beta cell identity markers resulted from an unexpected activation by harmine of an as-yet unidentified Target 2 that activates the protein kinase A (PKA) pathway. CONCLUSIONS/
interpretationThese findings make it clear that all DYRK1A inhibitors are not interchangeable. Those that drive both beta cell proliferation and identity/function will likely be preferable for diabetes therapy. Unravelling the mechanisms controlling the complex harmine-PKA-DYRK1A interactome will provide fruitful ground for future studies.
Indexed as
Identifiers
42766004What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.