Insulin-Stimulated Glucose Uptake Occurs in Specialized Cells within the Cumulus Oocyte Complex

Abstract

The oocyte exists within the mammalian follicle surrounded by somatic cumulus cells. These cumulus cells metabolize the majority of the glucose within the cumulus oocyte complex and provide energy substrates and intermediates such as pyruvate to the oocyte. The insulin receptor is present in cumulus cells and oocytes; however, it is unknown whether insulin-stimulated glucose uptake occurs in either cell type. Insulin-stimulated glucose uptake is thought to be unique to adipocytes, skeletal and cardiac muscle, and the blastocyst. Here, we show for the first time that many of the components required for insulin signaling are present in both cumulus cells and oocytes. We performed a set of experiments on mouse cumulus cells and oocytes and human cumulus cells using the nonmetabolizable glucose analog 2-deoxy-d-glucose to measure basal and insulin-stimulated glucose uptake. We show that insulin-stimulated glucose uptake occurs in both compact and expanded cumulus cells of mice, as well as in human cumulus cells. Oocytes, however, do not display insulin-stimulated glucose uptake. Insulin-stimulated glucose uptake in cumulus cells is mediated through phosphatidylinositol 3-kinase signaling as shown by inhibition of insulin-stimulated glucose uptake and Akt phosphorylation with the specific phosphatidylinositol 3-kinase inhibitor, LY294002. To test the effect of systemic in vivo insulin resistance on insulin sensitivity in the cumulus cell, cumulus cells from high fat-fed, insulin-resistant mice and women with polycystic ovary syndrome were examined. Both sets of cells displayed blunted insulin-stimulated glucose uptake. Our studies identify another tissue that, through a classical insulin-signaling pathway, demonstrates insulin-stimulated glucose uptake. Moreover, these findings suggest insulin resistance occurs in these cells under conditions of systemic insulin resistance.