Insulin Stimulates PI3K/AKT and Cell Adhesion to Promote the Survival of Individualized Human Embryonic Stem Cells

Abstract

Insulin is present in most maintenance media for human embryonic stem cells (hESCs), but little is known about its essential role in the cell survival of individualized cells during passage. In this article, we show that insulin suppresses caspase cleavage and apoptosis after dissociation. Insulin activates insulin‐like growth factor (IGF) receptor and PI3K/AKT cascade to promote cell survival and its function is independent of rho‐associated protein kinase regulation. During niche reformation after passaging, insulin activates integrin that is essential for cell survival. IGF receptor colocalizes with focal adhesion complex and stimulates protein phosphorylation involved in focal adhesion formation. Insulin promotes cell spreading on matrigel‐coated surfaces and suppresses myosin light chain phosphorylation. Further study showed that insulin is also required for the cell survival on E‐cadherin coated surface and in suspension, indicating its essential role in cell–cell adhesion. This work highlights insulin's complex roles in signal transduction and niche re‐establishment in hESCs. stem cells 2019;37:1030–1041

IL‐10 induces MC3T3‐E1 cells differentiation towards osteoblastic fate in murine model

“…Activated IGF1R is involved in cell growth and survival and influences an array of physiological and pathological conditions . For example, IGF1R inhibition is an escape mechanism in Ewing sarcoma and IGF1R inhibitors are candidate therapies for this disease . In this study, we found that IGF1R interacts with miR‐7025‐5p and that the down‐regulation of miR‐7025‐5p increases the IGF1R mRNA levels to promote osteogenic processes.…”

“…[29][30][31] For example, IGF1R inhibition is an escape mechanism in Ewing sarcoma and IGF1R inhibitors are candidate therapies for this disease. 32 In this study, we found that IGF1R interacts with miR-7025-5p and that the down-regulation of miR-7025-5p increases the IGF1R mRNA levels to promote osteogenic processes. Moreover, we found the levels of IGF1R and miR-7025-5p remain stable during osteogenic differentiation, but the expression of the IGF1R protein increases during fracture healing, whilst the levels of miR-7025-5p decline.…”

Endogenous IGF Signaling Directs Heterogeneous Mesoderm Differentiation in Human Embryonic Stem Cells

“…The IGF and insulin activate the PI3K and CK2 cascades, and they are essential for hPSC maintenance (Bendall et al, 2007;Chen et al, 2011;Godoy-Parejo et al, 2019;Wang et al, 2007). This study reveals the temporal regulation of IGFs on mesodermal differentiation ( Figure S4P).…”

“…The PI3K/AKT cascade is often discussed in stem cell regulation. PI3K/AKT activation is essential to suppress caspase and cell death in hESC maintenance (Godoy-Parejo et al, 2019). During differentiation, the insulin/IGF activates the PI3K cascade to promote neuroectoderm lineage while suppressing endoderm cell fate determination (Yu and Cui, 2016).…”

The apelin-13 peptide protects the heart against apoptosis through the ERK/MAPK and PI3K/AKT signaling pathways.

“…PI (3,4,5) P3 is an intracellular second messenger in the cell that needs to transfer protein kinase B (AKT) to the membrane for activation [34]. Phosphorylated AKT mediates insulin and various growth factors to induce cell growth and promote cell survival through numerous channels [35]. ERK/MAPK is a classical signaling pathway of anti-apoptosis.…”