Home Blog of Signal Transduction Protein Tyrosine Kinase IGF-1R The energy sensing LKB1-AMPKα1 pathway regulates IGF1 secretion and consequent activation of the IGF1R-PKB pathway in primary hepatocytes

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The energy sensing LKB1-AMPKα1 pathway regulates IGF1 secretion and consequent activation of the IGF1R-PKB pathway in primary hepatocytes

The insulin-like growth factor 1 (IGF1) pathway has been linked with various diseases including diabetes, cancer and aging. In contrast to the well-established regulatory mechanisms controlling IGF1 expression, molecular mechanisms regulating its secretion are not fully understood. The AMP-activated protein kinase (AMPK) is a key energy sensor, and cumulative evidence shows that it is an attractive therapeutic target for treatment of diabetes, cancer and aging. Here we found that deficiency of AMPK promoted IGF1 secretion in mouse primary hepatocytes. Furthermore, we found that AMPKα1 but not AMPKα2 was involved in regulation of IGF1 secretion in mouse primary hepatocytes. Knockout of AMPK caused activation of the IGF1 receptor (IGF1R)-protein kinase B (PKB; also known as Akt) pathway in hepatocytes, which was mediated by hypersecretion of IGF1. Upstream of AMPK, liver kinase B1 (LKB1) was responsible for AMPK-dependent suppression of IGF1 secretion in hepatocytes. Collectively, these findings demonstrate that the energy-sensing LKB1-AMPK pathway regulates IGF1 secretion in mouse primary hepatocytes, which in turn regulates activation of the IGF1R-PKB pathway.

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S7668 Picropodophyllin (PPP) Picropodophyllin (PPP, AXL1717) is a IGF-1R inhibitor with IC50 of 1 nM. It displays selectivity for IGF-1R and does not coinhibit tyrosine phosphorylation the IR, or of a selected panel of receptors less related to IGF-IR(FGF-R, PDGF-R, OR EGF-R). Picropodophyllin (PPP) induces apoptosis with antineoplastic activity.

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IGF-1R