Increased β‐site APP cleaving enzyme 1‐mediated insulin receptor cleavage in type 2 diabetes mellitus with cognitive impairment
| Autor: | Hong Bao, Yong Shen, Mengguo Zhang, Feng Gao, Weiwei Zhang, Dongmei Kang, Yuhao Ge, Zuolong Chen, Yiming Liu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Epidemiology Mutant Disease Cohort Studies Amyloid beta-Protein Precursor 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Insulin resistance Developmental Neuroscience Alzheimer Disease Internal medicine mental disorders Amyloid precursor protein Aspartic Acid Endopeptidases Humans Medicine Cognitive Dysfunction Aged Glycemic chemistry.chemical_classification biology business.industry Health Policy nutritional and metabolic diseases Type 2 Diabetes Mellitus Middle Aged medicine.disease Receptor Insulin Psychiatry and Mental health Insulin receptor 030104 developmental biology Endocrinology Enzyme Diabetes Mellitus Type 2 chemistry biology.protein Female Neurology (clinical) Amyloid Precursor Protein Secretases Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | Alzheimer's & Dementia. 17:1097-1108 |
| ISSN: | 1552-5279 1552-5260 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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