Stimulation of IRS-1-associated phosphatidylinositol 3-kinase and Akt/protein kinase B but not glucose transport by beta1-integrin signaling in rat adipocytes

UMMS Affiliation

Program in Molecular Medicine and Department of Biochemistry and Molecular Biology

Publication Date


Document Type



1-Phosphatidylinositol 3-Kinase; Adipocytes; Animals; Antigens, CD29; Biological Transport; Enzyme Activation; Glucose; Male; Oncogene Protein v-akt; Phosphoproteins; Phosphorylation; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Retroviridae Proteins, Oncogenic; *Signal Transduction; Tyrosine


Life Sciences | Medicine and Health Sciences


The signal transduction pathway by which insulin stimulates glucose transport is not understood, but a role for complexes of insulin receptor substrate (IRS) proteins and phosphatidylinositol (PI) 3-kinase as well as for Akt/protein kinase B (PKB) has been proposed. Here, we present evidence suggesting that formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation are insufficient to stimulate glucose transport in rat adipocytes. Cross-linking of beta1-integrin on the surface of rat adipocytes by anti-beta1-integrin antibody and fibronectin was found to cause greater IRS-1 tyrosine phosphorylation, IRS-1-associated PI 3-kinase activity, and Akt/PKB activation, detected by anti-serine 473 antibody, than did 1 nM insulin. Clustering of beta1-integrin also significantly potentiated stimulation of insulin receptor and IRS-1 tyrosine phosphorylation, IRS-associated PI 3-kinase activity, and Akt/PKB activation caused by submaximal concentrations of insulin. In contrast, beta1-integrin clustering caused neither a change in deoxyglucose transport nor an effect on the ability of insulin to stimulate deoxyglucose uptake at any concentration along the entire dose-response relationship range. The data suggest that (i) beta1-integrins can engage tyrosine kinase signaling pathways in isolated fat cells, potentially regulating fat cell functions and (ii) either formation of IRS-1/PI 3-kinase complexes and Akt/PKB activation is not necessary for regulation of glucose transport in fat cells or an additional signaling pathway is required.

DOI of Published Version



J Biol Chem. 1998 Dec 11;273(50):33119-22.

Journal/Book/Conference Title

The Journal of biological chemistry

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PubMed ID