Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin

Ritwik Datta, Carlos O. Lizama, Amin K. Soltani, William McKleroy, Michael J. Podolsky, Christopher D. Yang, Tony L. Huynh, Kelly M. Cautivo, Biao Wang, Suneil K. Koliwad, Nada A. Abumrad, Kamran Atabai

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The role of integrins, in particular αv integrins, in regulating insulin resistance is incompletely understood. We have previously shown that the αvβ5 integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) regulates cellular uptake of fatty acids. In this work, we evaluated the impact of MFGE8 on glucose homeostasis. We show that acute blockade of the MFGE8/β5 pathway enhances while acute augmentation dampens insulin-stimulated glucose uptake. Moreover, we find that insulin itself induces cell-surface enrichment of MFGE8 in skeletal muscle, which then promotes interaction between the αvβ5 integrin and the insulin receptor leading to dampening of skeletal-muscle insulin receptor signaling. Blockade of the MFGE8/β5 pathway also enhances hepatic insulin sensitivity. Our work identifies an autoregulatory mechanism by which insulin-stimulated signaling through its cognate receptor is terminated through up-regulation of MFGE8 and its consequent interaction with the αvβ5 integrin, thereby establishing a pathway that can potentially be targeted to improve insulin sensitivity.

Original languageEnglish
Article number2102171118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number18
StatePublished - May 4 2021


  • Insulin receptor
  • Insulin sensitivity
  • Insulin signaling
  • Integrins
  • MFGE8


Dive into the research topics of 'Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin'. Together they form a unique fingerprint.

Cite this