Materials and methods: LY2886721 was administered as a dietary supplement (0.02% wt/wt) for six consecutive weeks. Physiological, metabolic and motorassessments were performed during the last two weeks of treatment, followed by molecular tissue analyses post-mortem.
Results: LY2886721 treatment improved glucose homeostasis and hepatic gluconeogenesis in diabetic PLB4 mice, as determined by improvements in basal glucose and glucose/pyruvate tolerance tests. Furthermore, LY2886721 improved hepatic insulin sensitivity, as indicated by enhanced basal yperphosphorylation of insulin receptors. In PLB4 brains, we detected altered basal conditions of APP expression and processing, with beneficial effects on APP processing achieved by LY2886721 treatment. No improvements in motor coordination were found.
Conclusions: Our data provide support for a role of BACE1 as a regulator of systemic glucose homeostasis and suggest BACE1 inhibitors for the treatment of T2DMassociated pathologies, especially in cases where diabetes is comorbid to AD
|Number of pages||9|
|Journal||Biochimica et Biophysica Acta. Molecular Basis of Disease : BBA|
|Early online date||20 Apr 2021|
|Publication status||Published - 1 Jul 2021|
The authors would like to acknowledge University of Aberdeen PhD studentship to RD and Alzheimer’s Research UK grant to BP and MD (ARUK-PG2017B-11). The authors also thank David Riddell and David McKinzie at Eli Lilly for involvement with sample handling for Aβ determination.
- Beta Amyloid