ARHGAP21 Acts as an Inhibitor of the Glucose-Stimulated Insulin Secretion Process

Autor(es)

Ferreira, Sandra M. ^[1] ; Costa-Junior, Jose M. ^[1] ; Kurauti, Mirian A. ^[2] ; Leite, Nayara C. ^[1] ; Ortis, Fernanda ^[3] ; Rezende, Luiz F. ^[4] ; Barbosa, Helena C. ^[1] ; Boschero, Antonio C. ^[1] ; Santos, Gustavo J. ^[5]

Afiliação do(s) autor(es)

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

^[2] Univ State Maringa UEM, Dept Physiol Sci, Maringa, Parana - Brazil

^[3] Univ State Sao Paulo USP, Inst Biomed Sci, Dept Cellular Biol & Dev, Sao Paulo - Brazil

^[4] Univ State Montes Claros UNIMONTES, Dept Physiopathol, Montes Claros, MG - Brazil

^[5] Univ Fed Santa Catarina UFSC, Ctr Biol Sci, Dept Physiol Sci, Florianopolis, SC - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN ENDOCRINOLOGY; v. 11, NOV 26 2020.
• Citações Web of Science: 0

Resumo

ARHGAP21 is a RhoGAP protein implicated in the modulation of insulin secretion and energy metabolism. ARHGAP21 transient-inhibition increase glucose-stimulated insulin secretion (GSIS) in neonatal islets; however, ARHGAP21 heterozygote mice have a reduced insulin secretion. These discrepancies are not totally understood, and it might be related to functional maturation of beta cells and peripheral sensitivity. Here, we investigated the real ARHGAP21 role in the insulin secretion process using an adult mouse model of acute ARHGAP21 inhibition, induced by antisense. After ARHGAP21 knockdown induction by antisense injection in 60-day old male mice, we investigated glucose and insulin tolerance test, glucose-induced insulin secretion, glucose-induced intracellular calcium dynamics, and gene expression. Our results showed that ARHGAP21 acts negatively in the GSIS of adult islet. This effect seems to be due to the modulation of important points of insulin secretion process, such as the energy metabolism (PGC1 alpha), Ca2+ signalization (SYTVII), granule-extrusion (SNAP25), and cell-cell interaction (CX36). Therefore, based on these finds, ARHGAP21 may be an important target in Diabetes Mellitus (DM) treatment. (AU)

• Processo FAPESP: 11/12050-7 - Arhgap21 inibe a secreção de insulina e controla a homeostase glicêmica em camundongos
• Beneficiário: Sandra Mara Ferreira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 11/09012-6 - 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 em diferentes modelos celulares e animais
• Beneficiário: Antonio Carlos Boschiero
• Modalidade de apoio: Auxílio à Pesquisa - Temático