Research
Hormonal
Proinsulin acts as a selective ligand for the IR-A isoform, stimulating cell proliferation and migration with an affinity similar to IGF-2, thereby contributing to the mitogenic effects of hyperproinsulinemia.
High levels of proinsulin, often seen in early type 2 diabetes, are not just a byproduct of metabolic dysfunction but actively stimulate cell growth by binding to the IR-A receptor. This mechanism links metabolic disorders to increased cancer risk, suggesting that managing proinsulin levels is crucial for preventing proliferative diseases.
GoodSupportsHIGH confidence
Recently, proinsulin has been reported as an additional IR-A ligand. Proinsulin binds to IR-A with a similar affinity as IGF-2 (EC50 4.5±0.6 nM)... Similar to IGF-2, proinsulin effectively stimulates cell proliferation and migration.
Why this rating
Cites specific studies (Ref 6) establishing proinsulin as an IR-A ligand.
Source
Insulin Receptor Isoforms in Physiology and Disease: An Updated View
Antonino Belfiore et al. · Endocrine Reviews · 2017
DOI 10.1210/er.2017-00073
narrative_reviewCited 361×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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