Abstract
Inhibition of the lipid phosphatase SH2-domain containing inositol phosphatase 2 (SHIP2) in L6-C10 muscle cells, in 3T3-L1 adipocytes and in the liver of db/db mice has been shown to ameliorate insulin signal transduction and established SHIP2 as a negative regulator of insulin action. Here we show that SHIP2 inhibition in INS1E insulinoma cells increased Akt, glycogen synthase kinase 3 and extracellular signal-regulated kinases 1 and 2 phosphorylation. SHIP2 inhibition did not prevent palmitate-induced apoptosis, but increased cell proliferation. Our data raise the interesting possibility that SHIP2 inhibition exerts proliferative effects in beta-cells and further support the attractiveness of a specific inhibition of SHIP2 for the treatment of type 2 diabetes.
MeSH terms
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Apoptosis / drug effects
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Cell Proliferation / drug effects
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Cyclin A / genetics
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Cyclin A / metabolism
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Regulation, Enzymologic / drug effects
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Genes, Dominant
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Glycogen Synthase Kinase 3 / metabolism
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Humans
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Insulin / metabolism*
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Insulinoma / enzymology*
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Insulinoma / genetics
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Insulinoma / pathology*
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Mutant Proteins / metabolism
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Palmitic Acid / pharmacology
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Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
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Phosphoric Monoester Hydrolases / antagonists & inhibitors*
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Signal Transduction* / drug effects
Substances
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Cyclin A
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Insulin
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Mutant Proteins
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RNA, Messenger
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Palmitic Acid
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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Glycogen Synthase Kinase 3
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Phosphoric Monoester Hydrolases
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INPPL1 protein, human
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Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases