Phosphatidylinositol 3-Kinase Activity in 3T3-L1 Adipocytes: Effects of Pioglitazone on Insulin- and IGF-1-Stimulated Cells
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Authors
Sizer, Karen M.
Issue Date
1992
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Non-insulin dependent diabetes mellitus (NIDDM) is characterized by
insulin resistance in which insulin production may be near normal but
there is decreased insulin sensitivity in target tissues. Pioglitazone is a
drug recently shown to improve insulin sensitivity in insulin resistant cells
most likely by affecting an early event in insulin signal transduction. An
obligatory early event in insulin signal transduction is the activation of the
tyrosine kinase function of the insulin receptor. Substrates for the receptor
tyrosine kinase are not well characterized but appear to include
phosphatidylinositol 3-kinase (PI 3-kinase). In this study, the effects of
pioglitazone on insulin- and insulin-like growth factor-l (IGF-l)-induced
changes in PI 3-kinase activity in an adipocyte-like cell line (3T3-Ll) were
investigated. Adipocytes were treated with pioglitazone for 24 h before
stimulation with hormone and then PI 3-kinase activity was measured in
anti-phosphotyrosine immunoprecipitates prepared from cell lysates, using
phosphatidylinositol as substrate. Immunoprecipitable PI 3-kinase activity
increased 3 to l0-fold within 1 min of exposure to either insulin or IGF-l,
and remained elevated for at least 40 min. Half-maximal activity was
induced by both insulin or IGF-l at concentrations of about 5 nM. Maximal
effects of insulin and IGF-l were not additive. Pre-treatment of cells with
pioglitazone did not alter either basal PI 3-kinase activity or the sensitivity
and kinetics of increases induced by either insulin or IGF-l. In contrast,
pioglitazone pre-treatment reduced the attenuation by isoproterenol of
insulin-induced PI 3-kinase activity. These data suggest that pioglitazone
has no direct effect on insulin-stimulated PI 3-kinase, but may indirectly
facilitate this action of insulin by interfering with a mechanism which
normally antagonizes insulin-induced changes in PI 3-kinase.
With honors.
With honors.
Description
vii, 41 p.
Citation
Publisher
Kalamazoo College
License
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