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Life Sci. 2015 Apr 15;127:53-8. doi: 10.1016/j.lfs.2015.01.041. Epub 2015 Mar 2.

ARHGAP21 prevents abnormal insulin release through actin rearrangement in pancreatic islets from neonatal mice.

Author information

1
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
2
Department of Internal Medicine, School of Medical Science, Hematology and Hemotherapy Center - Hemocentro, INCT Sangue, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
3
Department of Structural and Functional Biology, Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil. Electronic address: bsampaio@unicamp.br.

Abstract

AIMS:

ARHGAP21 is a Rho GTPase-activating protein (RhoGAP) that associates with many proteins and modulates several cellular functions, including actin cytoskeleton rearrangement in different tissues. However, it is unknown whether ARHGAP21 is expressed in pancreatic beta cells and its function in these cells. Herein, we assess the participation of ARHGAP21 in insulin secretion.

MAIN METHODS:

Neonatal mice were treated with anti-sense oligonucleotide against ARHG AP21 (AS) for 2 days, resulting in a reduction of the protein's expression of about 60% in the islets. F-actin depolimerization, insulin secretion,mRNA level of genes involved in insulin secretion, maturation and proliferation were evaluated in islets from both control and AS-treated mice.

KEY FINDINGS:

ARHGAP21 co-localized with actin inMIN6 beta cells and with insulin in neonatal pancreatic islets. F-actin was reduced in AS-islets, as judged by lower phalloidin intensity. Insulin secretion was increased in islets from AS-treated mice, however no differences were observed in the GSIS (glucose-stimulated insulin secretion). In these islets, the pERK1/2 was increased, as well as the gene expressions of VAMP2 and SNAP25, proteins that are present in the secretory machinery. Maturation and cell proliferation were not affected in islets from AS-treated mice.

SIGNIFICANCE:

In conclusion, our data show, for the first time, that ARHGAP21 is expressed and participates in the secretory process of pancreatic beta cells. Its effect is probably via pERK1/2, which modulates the rearrangement of the cytoskeleton. ARHGAP21 also controls the expression of genes that encodes proteins of the secretory machinery.

KEYWORDS:

ARHGAP21; Actin rearrangement; Glucose; Insulin secretion

PMID:
25744409
DOI:
10.1016/j.lfs.2015.01.041
[Indexed for MEDLINE]

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