Prevention of tumour cell apoptosis associated with sustained protein kinase B phosphorylation is more sensitive to regulation by insulin signalling than stimulation of proliferation and extracellular signal-regulated kinase.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory study in human cancer cell lines without clinical or in vivo human data.
PubMed 28316059 · doi:10.1007/s11010-017-2996-y
What was done
The authors assessed the signaling, survival, and proliferative effects of insulin and IGF1 in Saos-2/B10 osteosarcoma and A549 lung carcinoma cell lines. ERK1/2 and Akt/PKB activation were measured by Western blotting, apoptosis inhibition by ELISA, and proliferation by [3H]-thymidine incorporation.
What was found
The abstract reports no exact numerical data. Both IGF1 and insulin stimulated proliferation and suppressed apoptosis, but regulation of apoptosis was more sensitive to hormone concentrations than stimulation of proliferation. Both hormones induced rapid and sustained Akt/PKB phosphorylation, whereas ERK1/2 activation occurred only with IGF1. Pharmacological inhibition or loss of Akt/PKB phosphorylation abolished the anti-apoptotic protection.
Why it matters
Insulin analogue safety testing often focuses on avoiding mitogenic ERK1/2 signaling while preserving Akt/PKB activation. These findings suggest that insulin-driven Akt/PKB activation alone can promote tumor progression by strongly enhancing cell survival at lower concentrations than required for mitogenesis.
Limits
The study is restricted to in vitro cancer cell lines and gives no quantitative effect sizes in the abstract. In vitro hormone exposures may not reflect in vivo tissue dynamics, drug clearance, or systemic physiological interactions in humans.
Cited by
- supports High sugar intake causes chronic hyperinsulinemia, which inhibits apoptosis in damaged or cancerous cells.