What question did this study set out to answer?

To determine the metabolic role of insulin receptor substrate-2 (IRS-2) in mediating insulin signaling, Glut4 translocation, and glucose uptake in brown adipocytes.

August 1, 2000Journal of Biological ChemistryOpen Access

Essential Role of Insulin Receptor Substrate-2 in Insulin Stimulation of Glut4 Translocation and Glucose Uptake in Brown Adipocytes

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Authors

MFMathias FaßhauerJustus-Liebig-Universität Gießen JKJohannes KleinNuffield Orthopaedic Centre KUKohjiro UekiInstitute for Security Studies

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Implication

In vitro study reveals impaired Glut4 translocation and glucose uptake in IRS-2-deficient brown adipocytes, highlighting an essential role for IRS-2 in targeted insulin signaling.

Key Points

To determine the metabolic role of insulin receptor substrate-2 (IRS-2) in mediating insulin signaling, Glut4 translocation, and glucose uptake in brown adipocytes.
Established brown adipocyte cell lines from wild-type and IRS-2 knockout (KO) mice and differentiated them into mature adipocytes in vitro.
Assessed insulin-stimulated glucose uptake, Glut4 translocation to the plasma membrane, and reconstitution via retroviral re-expression of IRS-2 or IRS-1.
Evaluated phosphatidylinositol (PI) 3-kinase activity, total Akt phosphorylation, downstream effector activation, and plasma membrane-associated Akt stimulation.
IRS-2 KO adipocytes showed a 50% decrease in insulin-induced glucose uptake due to impaired Glut4 plasma membrane translocation, which was partially rescued by IRS-2 re-expression but not IRS-1 overexpression.
IRS-2 KO cells demonstrated a total loss of IRS-2-associated PI 3-kinase activity and a 30% reduction in phosphotyrosine-associated PI 3-kinase activity (p < 0.05).
Total Akt activation and phosphorylation of GSK-3 and p70S6 kinase remained intact, but insulin stimulation of membrane-associated Akt was significantly decreased in KO cells.

Cite This Study

Faßhauer et al. (2000) studied this question.

synapsesocial.com/papers/6a6f751d2163a0a01bc3bfb3 https://doi.org/10.1074/jbc.m004046200

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Implication

In vitro study reveals impaired Glut4 translocation and glucose uptake in IRS-2-deficient brown adipocytes, highlighting an essential role for IRS-2 in targeted insulin signaling.

Essential Role of Insulin Receptor Substrate-2 in Insulin Stimulation of Glut4 Translocation and Glucose Uptake in Brown Adipocytes

Discussion

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Implication

Key Points

Cite This Study

Essential Role of Insulin Receptor Substrate-2 in Insulin Stimulation of Glut4 Translocation and Glucose Uptake in Brown Adipocytes

Discussion

Member takes

Implication

Key Points

Cite This Study

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