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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: FRONTIERS IN ENDOCRINOLOGY; v. 11, NOV 26 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 11/12050-7 - ARHGAP21 INHIBTS INSULIN SECRETION AND CONTROLS GLUCOSE HOMEOSTASE IN MICE
• Grantee: Sandra Mara Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/09012-6 - Molecular mechanisms involved in the dysfunction and death of pancreatic beta cells in Diabetes Mellitus: strategies for the prevention of islet dysfunction and for islet mass recuperation in different cellular and animal models
• Grantee: Antonio Carlos Boschiero
• Support Opportunities: Research Projects - Thematic Grants