Hormonal
The insulin receptor isoform IR-A, which binds IGF-2 and proinsulin, promotes cell proliferation and is associated with detrimental effects like cancer progression and insulin resistance when overexpressed in adult life, whereas IR-B is primarily responsible for metabolic regulation.
This research highlights that not all insulin signaling is the same. The IR-A isoform, which responds to IGF-2 and proinsulin, drives cell growth and is linked to cancer and insulin resistance when overactive in adults. In contrast, IR-B handles metabolic regulation. Future treatments may need to target specific isoforms to manage diabetes without promoting cancer risk, suggesting that precision medicine approaches are necessary for metabolic health.
High IR-A expression which is advantageous in prenatal life appears to be associated with detrimental effects, such as dysregulated cell proliferation and insulin resistance in adult life.
Why this rating
The paper is a comprehensive review citing multiple structural and functional studies, though it is not a primary clinical trial.
Source
Insulin Receptor Isoforms in Physiology and Disease: An Updated View
Antonino Belfiore et al. · Endocrine Reviews · 2017
DOI 10.1210/er.2017-00073
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