Hormonal
In Type 2 Diabetes, elevated circulating levels of microRNA-144 (miR-144) directly inhibit the expression of Insulin Receptor Substrate 1 (IRS1), thereby impairing insulin signaling and contributing to insulin resistance.
This research identifies a specific molecular mechanism in Type 2 Diabetes where high levels of miR-144 block insulin signaling by reducing IRS1. For patients, this highlights that insulin resistance is driven by specific genetic regulatory failures, not just lifestyle factors. While this paper does not offer a direct treatment, it identifies miR-144 as a potential biomarker for disease severity and a target for future therapies aimed at restoring insulin sensitivity.
Increased circulating level of miR-144 has been found to correlate with down-regulation of its predicted target, insulin receptor substrate 1 (IRS1) at both mRNA and protein levels. We could also experimentally demonstrate that IRS1 is indeed the target of miR-144.
Why this rating
Strong evidence combining human observational data (correlation in patients), animal models (rat tissues), and in vitro mechanistic validation (luciferase assays, cell transfection).
Source
MicroRNA 144 Impairs Insulin Signaling by Inhibiting the Expression of Insulin Receptor Substrate 1 in Type 2 Diabetes Mellitus
Dwi Setyowati Karolina et al. · PLoS ONE · 2011
DOI 10.1371/journal.pone.0022839
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