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Exosomes derived from pancreatic cancer cells induce insulin resistance in C2C12 myotube cells through the PI3K/Akt/FoxO1 pathway

ABSTRACT: Prospective epidemiological studies have consistently supported that pancreatic cancer associated new-onset diabetes mellitus (PC-DM) is probably an important clue for early diagnosis of pancreatic cancer (PC). However, the mechanism underlying remains fragmentary. In this study, two types of exosomes released by murine pancreatic cancer cells and murine pancreatic ductal epithelial cells were isolated，and their effects on skeletal muscle cells were invested. The results showed that PC-derived exosomes can readily enter C2C12 myotubes, and then induce lipidosis, glucose intake inhibition. We also found that PC-derived exosomes can inhibit Insulin and PI3K/Akt signaling, in which insulin-induced FoxO1 nuclear exclusion is preserved while Glut4 trafficking is impaired. In addition, further microarray and Kyoto encyclopedia of genes and genomes (KEGG) analysis prompted that exosomal microRNAs (miRNAs) probably play an critical role in this process, which also has been preliminarily demonstrated in vitro. Taking together, these results suggest that PC-derived exosomes induce insulin resistance (IR) of skeletal muscle cells through Insulin and PI3K/Akt/FoxO1 signaling pathway, and exosomal miRNAs are probably involved. The novel findings also support the theories of cancer “metabolic reprogramming” and “metabolic crosstalk”.

ORGANISM(S): Mus musculus

PROVIDER: GSE95741 | GEO | 2017/08/11

SECONDARY ACCESSION(S): PRJNA378249

REPOSITORIES: GEO

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Exosomes derived from pancreatic cancer cells induce insulin resistance in C2C12 myotube cells through the PI3K/Akt/FoxO1 pathway

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