Ceramide and glucosamine antagonism of alternate signaling pathways regulating insulin- and osmotic shock-induced glucose transporter 4 translocation

Steve F. Kralik, L. I U Ping, Brian J. Leffler, Jeffrey Elmendorf

Research output: Contribution to journalArticle

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Abstract

In addition to insulin, hyperosmolarity induces glucose transporter 4 (GLUT4) translocation in 3T3-L1 adipocytes. However, in contrast to insulin this stimulation is independent of PI3K/Akt. In this study we assessed whether ceramide and/or glucosamine, two known insulin-signaling antagonists, also affected the PI3K/Akt-independent signal. Insulin, but not hyperosmolarity, clearly increased the activities of PI3K and Akt. C2-ceramide did not alter insulin-stimulated PI3K activity, but did decrease the ability of insulin to activate Akt and GLUT4 translocation. Consistent with osmotic shock-mediated GLUT4 translocation being independent of PI3K/Akt, GLUT4 translocation induced by hyperosmolarity was not altered by C2-ceramide. In contrast to the specific C2-ceramide-induced attenuation of insulin-stimulated GLUT4 translocation, overexpression of glutamine:fructose-6-phosphate amidotransferase, the rate-limiting enzyme in the synthesis of UDP-N-acetylglucosamine, and/or pretreatment of cells with glucosamine, a precursor of UDP-N-acetylglucosamine, inhibited both insulin- and hyperosmolarity-stimulated GLUT4 translocation. Glucosamine did not alter any of the known proximal insulin signal transduction events. These data suggest that although the hyperosmolarity-induced signal bypasses the initial insulin signal transduction steps, it is likely to induce GLUT4 translocation through activation of a common convergent signal transduction step, targeted by UDP-N-acetylglucosamine, downstream of and/or in parallel to PI3K/Akt.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalEndocrinology
Volume143
Issue number1
DOIs
StatePublished - 2002

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Insulin Coma
Facilitative Glucose Transport Proteins
Ceramides
Glucosamine
Osmotic Pressure
Insulin
Phosphatidylinositol 3-Kinases
Uridine Diphosphate N-Acetylglucosamine
Signal Transduction
Insulin Antagonists
Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)
Adipocytes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Ceramide and glucosamine antagonism of alternate signaling pathways regulating insulin- and osmotic shock-induced glucose transporter 4 translocation. / Kralik, Steve F.; Ping, L. I U; Leffler, Brian J.; Elmendorf, Jeffrey.

In: Endocrinology, Vol. 143, No. 1, 2002, p. 37-46.

Research output: Contribution to journalArticle

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