Tags

Type your tag names separated by a space and hit enter

Rescuing 3T3-L1 adipocytes from insulin resistance induced by stimulation of Akt-mammalian target of rapamycin/p70 S6 kinase (S6K1) pathway and serine phosphorylation of insulin receptor substrate-1: effect of reduced expression of p85alpha subunit of phosphatidylinositol 3-kinase and S6K1 kinase.
Endocrinology. 2009 Mar; 150(3):1165-73.E

Abstract

Phosphorylation of insulin receptor substrate-1 (IRS-1) on serine residues has been recognized as a mechanism responsible for a diminution of insulin action and insulin resistance. Potential approaches to improve insulin sensitivity may include interference with and/or reduction in expression of certain signaling intermediates that participate in the pathogenesis of insulin resistance. In this study, we transduced fully differentiated 3T3-L1 adipocytes with a constitutively active myristoylated Akt that led to hyperactivation of mammalian target of rapamycin and p70 S6 kinase (S6K1), increased serine phosphorylation of IRS-1, and reduction in insulin-stimulated phosphatidylinositol (PI) 3-kinase activity and glucose transport. We then reduced expression of the PI 3-kinase regulatory subunit, p85alpha, or expression of S6K1 kinase using small interfering RNA transfections, which led to a reduction in p85alpha expression of 70% at 48 h (P < 0.05) and S6K1 of 49% (P < 0.05). Reduction in expression of either p85alpha or S6K1 achieved with small interfering RNA in the presence of myristoylated Akt rescued 3T3-L1 adipocytes from the insulin resistance induced by serine phosphorylation of IRS-1 and completely restored insulin-stimulated activation of PI 3-kinase and glucose uptake. We conclude that reduction in expression of p85alpha or S6K1 could represent therapeutic targets to mitigate insulin resistance.

Authors+Show Affiliations

Department of Veterans Affairs, University of Colorado Denver, Aurora, Colorado 80045, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

18948408

Citation

Adochio, Rebecca, et al. "Rescuing 3T3-L1 Adipocytes From Insulin Resistance Induced By Stimulation of Akt-mammalian Target of Rapamycin/p70 S6 Kinase (S6K1) Pathway and Serine Phosphorylation of Insulin Receptor Substrate-1: Effect of Reduced Expression of P85alpha Subunit of Phosphatidylinositol 3-kinase and S6K1 Kinase." Endocrinology, vol. 150, no. 3, 2009, pp. 1165-73.
Adochio R, Leitner JW, Hedlund R, et al. Rescuing 3T3-L1 adipocytes from insulin resistance induced by stimulation of Akt-mammalian target of rapamycin/p70 S6 kinase (S6K1) pathway and serine phosphorylation of insulin receptor substrate-1: effect of reduced expression of p85alpha subunit of phosphatidylinositol 3-kinase and S6K1 kinase. Endocrinology. 2009;150(3):1165-73.
Adochio, R., Leitner, J. W., Hedlund, R., & Draznin, B. (2009). Rescuing 3T3-L1 adipocytes from insulin resistance induced by stimulation of Akt-mammalian target of rapamycin/p70 S6 kinase (S6K1) pathway and serine phosphorylation of insulin receptor substrate-1: effect of reduced expression of p85alpha subunit of phosphatidylinositol 3-kinase and S6K1 kinase. Endocrinology, 150(3), 1165-73. https://doi.org/10.1210/en.2008-0437
Adochio R, et al. Rescuing 3T3-L1 Adipocytes From Insulin Resistance Induced By Stimulation of Akt-mammalian Target of Rapamycin/p70 S6 Kinase (S6K1) Pathway and Serine Phosphorylation of Insulin Receptor Substrate-1: Effect of Reduced Expression of P85alpha Subunit of Phosphatidylinositol 3-kinase and S6K1 Kinase. Endocrinology. 2009;150(3):1165-73. PubMed PMID: 18948408.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rescuing 3T3-L1 adipocytes from insulin resistance induced by stimulation of Akt-mammalian target of rapamycin/p70 S6 kinase (S6K1) pathway and serine phosphorylation of insulin receptor substrate-1: effect of reduced expression of p85alpha subunit of phosphatidylinositol 3-kinase and S6K1 kinase. AU - Adochio,Rebecca, AU - Leitner,J Wayne, AU - Hedlund,Reed, AU - Draznin,Boris, Y1 - 2008/10/23/ PY - 2008/10/25/pubmed PY - 2009/3/25/medline PY - 2008/10/25/entrez SP - 1165 EP - 73 JF - Endocrinology JO - Endocrinology VL - 150 IS - 3 N2 - Phosphorylation of insulin receptor substrate-1 (IRS-1) on serine residues has been recognized as a mechanism responsible for a diminution of insulin action and insulin resistance. Potential approaches to improve insulin sensitivity may include interference with and/or reduction in expression of certain signaling intermediates that participate in the pathogenesis of insulin resistance. In this study, we transduced fully differentiated 3T3-L1 adipocytes with a constitutively active myristoylated Akt that led to hyperactivation of mammalian target of rapamycin and p70 S6 kinase (S6K1), increased serine phosphorylation of IRS-1, and reduction in insulin-stimulated phosphatidylinositol (PI) 3-kinase activity and glucose transport. We then reduced expression of the PI 3-kinase regulatory subunit, p85alpha, or expression of S6K1 kinase using small interfering RNA transfections, which led to a reduction in p85alpha expression of 70% at 48 h (P < 0.05) and S6K1 of 49% (P < 0.05). Reduction in expression of either p85alpha or S6K1 achieved with small interfering RNA in the presence of myristoylated Akt rescued 3T3-L1 adipocytes from the insulin resistance induced by serine phosphorylation of IRS-1 and completely restored insulin-stimulated activation of PI 3-kinase and glucose uptake. We conclude that reduction in expression of p85alpha or S6K1 could represent therapeutic targets to mitigate insulin resistance. SN - 1945-7170 UR - https://www.unboundmedicine.com/medline/citation/18948408/Rescuing_3T3_L1_adipocytes_from_insulin_resistance_induced_by_stimulation_of_Akt_mammalian_target_of_rapamycin/p70_S6_kinase__S6K1__pathway_and_serine_phosphorylation_of_insulin_receptor_substrate_1:_effect_of_reduced_expression_of_p85alpha_subunit_of_phosphatidylinositol_3_kinase_and_S6K1_kinase_ L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2008-0437 DB - PRIME DP - Unbound Medicine ER -