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

Author(s):Show less -

Zangerolamo, Lucas ^[1] ; Vettorazzi, Jean F. ^[2] ; Solon, Carina ^[3] ; Bronczek, Gabriela A. ^[1] ; Engel, Daiane F. ^[3] ; Kurauti, Mirian A. ^[4] ; Soares, Gabriela M. ^[1] ; Rodrigues, Karina S. ^[1] ; Velloso, Licio A. ^[3] ; Boschero, Antonio C. ^[1] ; Carneiro, Everardo M. ^[1] ; Barbosa, Helena C. L. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Obes & Comorbid Res Ctr, Dept Struct & Funct Biol, UNICAMP, Campinas, SP - Brazil

^[2] UNIVEL, Educ Union Cascavel, Cascavel, Parana - Brazil

^[3] Univ Estadual Campinas, Obes & Comorbid Res Ctr, Lab Cell Signaling, UNICAMP, Campinas, SP - Brazil

^[4] Univ Estadual Maringa, Dept Physiol Sci, UEM, Maringa, Parana - Brazil

• Document type: Journal article
• Source: Molecular and Cellular Endocrinology; v. 521, FEB 5 2021.
• Web of Science Citations: 0

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder and the major cause of dementia. According to predictions 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 beta-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 beta-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 homeostasis disturbance in AD pathology. (AU)

• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass
• Grantee: Antonio Carlos Boschiero
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/13410-3 - Possible contribution of tauroursodeoxycholic acid (TUDCA) on the remission of type 2 diabetes in mice submitted to Duodenal-Jejunal Bypass
• Grantee: Jean Franciesco Vettorazzi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/23729-1 - Molecular mechanisms of the ARHGAP21 RhoGAP in the VLDL vesicles formation in hepatocytes of ARHGAP21-heterozygous C57BL/6 mice
• Grantee: Lucas Zangerolamo
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/06363-1 - Therapeutic potential of GHRH and metformin on pancreatic beta cell function against endoplasmic reticulum stress and type 2 diabetes mellitus progress
• Grantee: Helena Cristina de Lima Barbosa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/20213-2 - Role of TUDCA bile acid in the glycemic and energetic metabolism of mice with Alzheimer's and senile
• Grantee: Lucas Zangerolamo
• Support Opportunities: Scholarships in Brazil - Master