|Support type:||Scholarships in Brazil - Scientific Initiation|
|Effective date (Start):||February 01, 2020|
|Effective date (End):||September 30, 2021|
|Field of knowledge:||Biological Sciences - Physiology - Physiology of Organs and Systems|
|Principal Investigator:||Helena Cristina de Lima Barbosa Sampaio|
|Grantee:||Amanda Pellison Nascimento|
|Home Institution:||Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil|
Type 2 diabetes mellitus (DM2) is a metabolic disease that increasingly affects populations worldwide, mainly due to changes in lifestyles, which lead to changes in dietary intake. Such changes raise the rates of obesity and, with it, the obesity-associated problems. DM2 can be characterized by the failure of pancreatic beta cells due initially to the peripheral resistance to the hormone insulin, which results in its supersecret and, therefore, beta-cell hyperfunction, leading to islet cell death processes. Also, glucagon plays an important role in the pathogenesis of DM2, since fasting hyperglucagonemia is present, and when diabetic patients are fed, the levels of this hormone do not decrease as in control populations, which contributes to the high glycemia characteristic of DM2. High glycemia and resistance of cells to the signaling of hormones related to glycemic metabolism contribute to the manifestation of systemic complications, some of them associated to the central nervous system in the occurrence of Alzheimer's disease (AD). AD can be classified as a neurodegenerative disease, caused by the extracellular accumulation of ²-amyloid protein in the hippocampus. In addition, recent studies show that in AD there is resistance to insulin in the central nervous system, as well as a reduction in glucose uptake and impairment in energy metabolism in other systems. In this scenario, tauroursodeoxycholic bile acid (TUDCA) has been researched in metabolic and neurodegenerative disease models, because it presents antiapoptotic effects and reduces reticulum stress since it acts as a chemical chaperone. In addition, TUDCA activates signaling pathways associated with insulin and glucagon. However, the pathways associated mainly with glucagon are not completely elucidated. Thus, we propose in this project to evaluate the glucagon signaling in a mouse model with AD, as well as the possible protective effect of TUDCA on the consequent hepatic alterations in AD. A better understanding of the complications of glycemic metabolism in both DM2 and AD may contribute to more effective therapies in the treatment of both diseases.