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Increased β-site APP cleaving enzyme 1-mediated insulin receptor cleavage in type 2 diabetes mellitus with cognitive
Hong Bao1, Yiming Liu1, Mengguo Zhang1
1Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Introduction:
Patients with type 2 diabetes mellitus (T2DM) are at a high risk of cognitive impairment, with insulin resistance playing a pivotal role. β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is considered a predictor of Alzheimer's disease. However, the potential roles of BACE1 in insulin resistance and the risk of cognitive impairment in T2DM remain unclear.
Methods:
We measured plasma BACE1 levels, BACE1 cleavage activities for Swedish mutant amyloid precursor protein (APPsw) and insulin receptor β subunit (INSR-β), and soluble INSR (sINSR) levels in a clinical cohort study.
Results:
T2DM patients with or without cognitive impairment exhibited elevated plasma BACE1 levels and BACE1 enzymatic activities for APPsw and INSR-β, and sINSR levels. Moreover, the glycemic status correlated with elevated BACE1 levels and BACE1-mediated INSR cleavage, which was associated with insulin resistance.
Discussion:
The elevated BACE1 levels in T2DM may contribute to increasing the cognitive impairment risk through both amyloidogenesis and insulin resistance.
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