Augmented β-Cell Function and Mass in Glucocorticoid-Treated Rodents Are Associated with Increased Islet Ir-β/AKT/mTOR and Decreased AMPK/ACC and AS160 Signaling
Figure 7
Hypothetical scheme of the main signaling pathways modulated in pancreatic β-cells by the in vivo glucocorticoid treatment. Decreased insulin sensitivity in peripheral tissues leads to hyperinsulinemia, which stimulates the insulin signaling in the pancreatic β-cell. Activated AKT inactivates the AS160, releasing its inhibitory effect on insulin secretion (functional compensation). Also, pAKT activates mTOR, favoring β-cell growth (structural compensation). In parallel, dephosphorylated AMPK, which may reflect a low AMP : ATP ratio, favors the activation of mTOR by AKT and suggest that AS160 inhibition is modulated by the insulin signaling, rather than AMPK signaling. An increased parasympathetic drive through muscarinic receptor (M3) and/or increased β-cells communication, through CX36 channels, may increase cytosolic Ca2+ and activates PKC, which stimulates insulin secretion. represents stimulations and represents inhibition.
