Peripheral Aβ acts as a negative modulator of insulin secretion

Abstract

Significance The cerebral accumulation of amyloid β (Aβ) is a hallmark of Alzheimer’s disease (AD). While type 2 diabetes mellitus is known to be a risk factor for AD, the underlying mechanisms remain unclear. In the present study, we demonstrate that plasma Aβ is produced from glucose- and insulin-susceptible peripheral tissues, such as the pancreas, adipose tissues, skeletal muscles, and liver, to inhibit insulin secretion from islet β-cells. Our findings suggest a physiological role of peripheral Aβ in glucose and insulin metabolism and a possible mechanism linking diabetes to AD. In addition, although plasma Aβ levels are currently used as a diagnostic biomarker of AD, our data suggest they should be used with caution.