11 research outputs found
The beta secretase BACE1 regulates the expression of insulin receptor in the liver
Insulin receptor (IR) plays a key role in the control of glucose homeostasis; however, the regulation of its cellular expression remains poorly understood. Here we show that the amount of biologically active IR is regulated by the cleavage of its ectodomain, by the β-site amyloid precursor protein cleaving enzyme 1 (BACE1), in a glucose concentration-dependent manner. In vivo studies demonstrate that BACE1 regulates the amount of IR and insulin signaling in the liver. During diabetes, BACE1-dependent cleavage of IR is increased and the amount of IR in the liver is reduced, whereas infusion of a BACE1 inhibitor partially restores liver IR. We suggest the potential use of BACE1 inhibitors to enhance insulin signaling during diabetes. Additionally, we show that plasma levels of cleaved IR reflect IR isoform A expression levels in liver tumors, which prompts us to propose that the measurement of circulating cleaved IR may assist hepatic cancer detection and management
Immunological Origin and Functional Properties of Catalytic Autoantibodies to Amyloid β Peptide
A Peptide Binding to the β-Site of APP Improves Spatial Memory and Attenuates Aβ Burden in Alzheimer’s Disease Transgenic Mice
C-Terminal Tetrapeptides Inhibit Aβ42-Induced Neurotoxicity Primarily through Specific Interaction at the N-Terminus of Aβ42
Familial Alzheimer A2 V Mutation Reduces the Intrinsic Disorder and Completely Changes the Free Energy Landscape of the Aβ1–28 Monomer
Amyloid beta Protein and Alzheimer's Disease: When Computer Simulations Complement Experimental Studies
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