The Bile Acid TUDCA Improves Beta-Cell Mass and Reduces Insulin Degradation in Mice With Early-Stage of Type-1 Diabetes

Autor(es)

Bronczek, Gabriela Alves ^{[1, 2]} ; Vettorazzi, Jean Franciesco ^[1] ; Soares, Gabriela Moreira ^[1] ; Kurauti, Mirian Ayumi ^[1] ; Santos, Cristiane ^[1] ; Bonfim, Maressa Fernandes ^[1] ; Carneiro, Everardo Magalhaes ^[1] ; Balbo, Sandra Lucinei ^[2] ; Boschero, Antonio Carlos ^[1] ; Costa Jonior, Jose Maria ^[1]

Afiliação do(s) autor(es)

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

^[2] Western Parana State Univ UNIOESTE, Lab Endocrine Physiol & Metab, Biol Sci & Hlth Ctr, Cascavel - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN PHYSIOLOGY; v. 10, MAY 15 2019.
• Citações Web of Science: 1

Resumo

Type 1 diabetes (T1D) is characterized by impairment in beta-cell mass and insulin levels, resulting in hyperglycemia and diabetic complications. Since diagnosis, appropriate control of glycaemia in T1D requires insulin administration, which can result in side effects, such as hypoglycemia. In this sense, some bile acids have emerged as new therapeutic targets to treat T1D and T2D, as well as metabolic diseases. The taurine conjugated bile acid, tauroursodeoxycholic (TUDCA) reduces the incidence of T1D development and improves glucose homeostasis in obese and T2D mice. However, its effects in early-stage of T1D have not been well explored. Therefore, we have assessed the effects of TUDCA on the glycemic control of mice with early-stage T1D. To achieve this, C57BL/6 mice received intraperitoneal administration of streptozotocin (STZ, 40 mg/kg) for 5 days. Once diabetes was confirmed in the STZ mice, they received TUDCA treatment (300 mg/kg) or phosphate buffered saline (PBS) for 24 days. After 15 days of treatment, the STZ+TUDCA mice showed a 43% reduction in blood glucose, compared with the STZ group. This reduction was likely due to an increase in insulinemia. This increase in insulinemia may be explained, at least in part, by a reduction in hepatic IDE activity and, consequently, reduction on insulin clearance, as well as an increase in beta-cell mass and a higher beta-cell number per islet. Also, the groups did not present any alterations in insulin sensitivity. All together, these effects contributed to the improvement of glucose metabolism in T1D mice, pointing TUDCA as a potential therapeutic agent for the glycemic control in early-stage of T1D. (AU)

• Processo FAPESP: 17/13410-3 - Possível Contribuição do ácido tauroursodesoxicólico (TUDCA) sobre a remissão do Diabetes tipo 2 em camundongos submetidos a Derivação Duodeno Jejunal
• Beneficiário: Jean Franciesco Vettorazzi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/12611-0 - Mecanismos moleculares envolvidos na disfunção e morte de células beta pancreáticas no Diabetes mellitus: estratégias para a inibição desses processos e para a recuperação da massa insular
• Beneficiário: Antonio Carlos Boschiero
• Modalidade de apoio: Auxílio à Pesquisa - Temático