The bile acid TUDCA improves glucose metabolism in streptozotocin-induced Alzheimer’s disease mice model.

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder and the major cause of dementia. According to pre- dictions of the World Health Organization, more than 150 million people worldwide will suffer from dementia by

2050. An increasing number of studies have associated AD with type 2 diabetes mellitus (T2DM), since most of the features found in T2DM are also observed in AD, such as insulin resistance and glucose intolerance. In this sense, some bile acids have emerged as new therapeutic targets to treat AD and metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic (TUDCA), reduces amyloid oligomer accumulation and improves cognition in APP/PS1 mice model of AD, and also improves glucose-insulin homeostasis in obese and type 2 diabetic mice. Herein, we investigated the effect of TUDCA upon glucose metabolism in streptozotocin-induced AD mice model (Stz). The Stz mice that received 300 mg/kg TUDCA during 10 days (Stz + TUDCA), showed improvement in glucose tolerance and insulin sensitivity, reduced fasted and fed glycemia, increased islet mass and β-cell area, as well as increased glucose-stimulated insulin secretion, compared with Stz mice that received only PBS. Stz + TUDCA mice also displayed lower neuroinflammation, reduced protein content of amyloid oligomer in the hippocampus, improved memory test and increased protein content of insulin receptor β-subunit

in the hippocampus. In conclusion, TUDCA treatment enhanced glucose homeostasis in the streptozotocin- induced Alzheimer’s disease mice model, pointing this bile acid as a good strategy to counteract glucose ho- meostasis disturbance in AD pathology.