The researchers further showed that the mice without Akt1 displayed a four-fold reduction in milk secretion compared to either normal mice or mice lacking Akt2.
The findings represent some of the first to reveal functional differences between Akt1 and Akt2, the researchers said. The new findings show that Akt1 is uniquely essential for lactation and establish a role for the isoform in glucose metabolism, a function earlier linked almost exclusively to Akt2, they said.
The findings may have important implications for cancer therapy, as the Akt pathway is also one of the most commonly activated in cancer, Chodosh said.
“The metabolic demands of the lactating mammary epithelial cell bear many similarities to those of tumor cells in that pathways controlling energy generation as well as carbohydrate, protein, and lipid synthesis must be coordinated to support the anabolic processes central to growth,?the researchers wrote. “In this regard, Akt1’s ability to act as a central regulator of nutrient uptake and utilization is consistent with the frequent observation of constitutive activation of the PI3K/AKT pathway in a wide range of human cancers, including those of the breast.?
Cancer cells also commonly exhibit increased rates of glucose uptake as part of a shift toward a greater reliance on that sugar’s breakdown for energy, a phenomenon known as the Warburg effect. Such increased glycolytic metabolism in tumors is associated with increased tumor aggressiveness and poor prognosis, the researchers said.
“Our findings demonstrating a physiological requirement for Akt1 in the control of glucose and lipid metabolism further implicate Akt1 activation as a potential mediator of the Warburg effect and reinforce the importance of efforts to design pharmacologic agents that will inhibit this pathway in tumors.?