BACE1 Inhibition Protects Against Type 2 Diabetes Mellitus by Restoring Insulin Receptor in Mice
Abstract
1. Introduction
2. Results
2.1. Elevated BACE1 Protein Levels and Enzyme Activity in Liver and Brain Form WT-HFD Mice
2.2. BACE1 Overexpression Caused Reduced Liver InsR Level and Diabetic Phenotypes in HUBC Mice
2.3. Elenbecestat Treatment Improved Glucose Tolerance and Insulin Sensitivity in HFD Mice
2.4. Elenbecestat Treatment Restored Hepatic Insulin Receptor Levels and Its Downstream Pathway in HFD Mice
2.5. Elenbecestat Treatment Ameliorated Cognitive Impairment and Anxiety Behavior in HFD Mice
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. High-Fat Diet Treatments
4.3. Drug Treatments
4.4. Metabolic Measurements
4.5. Western Blotting
4.6. Oil Red O (ORO) Staining
4.7. BACE1 Enzyme Activity Assay
4.8. Immunofluorescence Staining
4.9. Serum Biochemical Analysis
4.10. Behavior Tests
4.11. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
BACE1 | Β-secretase 1 |
AD | Alzheimer’s disease |
T2DM | Type 2 diabetes mellitus |
HFD | High-fat diet |
HUBC | Systemic overexpression of bace1 |
InsR | Insulin receptor |
App | Amyloid precursor protein |
WT | Wild-type |
Ele | Elenbecestat |
NCD | Normal chow diet |
GTT | Glucose tolerance test |
ITT | Insulin tolerance test |
ORO | Oil Red O |
BCA | Bicinchonic acid |
NGS | Normal goat serum |
LDL | Low-density lipoprotein |
TG | Triglycerides |
AUC | Area under the curve |
WAT | White adipose tissue |
ns | No significant differences |
HDL | High-density lipoprotein |
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Lin, T.; Liang, T.; Shen, Y.; Gao, F. BACE1 Inhibition Protects Against Type 2 Diabetes Mellitus by Restoring Insulin Receptor in Mice. Int. J. Mol. Sci. 2025, 26, 5100. https://doi.org/10.3390/ijms26115100
Lin T, Liang T, Shen Y, Gao F. BACE1 Inhibition Protects Against Type 2 Diabetes Mellitus by Restoring Insulin Receptor in Mice. International Journal of Molecular Sciences. 2025; 26(11):5100. https://doi.org/10.3390/ijms26115100
Chicago/Turabian StyleLin, Tingting, Ting Liang, Yong Shen, and Feng Gao. 2025. "BACE1 Inhibition Protects Against Type 2 Diabetes Mellitus by Restoring Insulin Receptor in Mice" International Journal of Molecular Sciences 26, no. 11: 5100. https://doi.org/10.3390/ijms26115100
APA StyleLin, T., Liang, T., Shen, Y., & Gao, F. (2025). BACE1 Inhibition Protects Against Type 2 Diabetes Mellitus by Restoring Insulin Receptor in Mice. International Journal of Molecular Sciences, 26(11), 5100. https://doi.org/10.3390/ijms26115100