Fig. 5.

Aβ-mediated crosstalk of peripheral tissues in glucose and insulin homeostasis. Increased levels of blood glucose (green) after food intake trigger insulin (blue) secretion from islet β-cells. This glucose-triggered insulin secretion is accompanied with Aβ (red) secretion from the same β-cells, a phenomenon we call ‘the primary secretion’ of Aβ. Secreted insulin acts on insulin-targeted organs to promote glucose uptake by adipose tissues and muscles and glycogen synthesis in muscles and the liver. These tissues release their own endocrine factors (i.e., organokines, including adipokines, myokines, and hepatokines) upon insulin stimulation to maintain glucose and lipid homeostasis and insulin sensitivity in an autocrine, paracrine, and endocrine manner. This insulin-dependent secretion of organokines coincides with Aβ secretion from the same cells, a phenomenon we called ‘the secondary secretion’ of Aβ. The secreted Aβ acts on β-cells in an autocrine and endocrine manner to negatively modulate insulin secretion.