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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Whole body ARHGAP21 reduction improves glucose homeostasis in high-fat diet obese mice

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Soares, Gabriela M. [1] ; Zangerolamo, Lucas [1] ; Azevedo, Elis G. [1] ; Costa-Junior, Jose M. [1] ; Carneiro, Everardo M. [1] ; Saad, Sara T. [2] ; Boschero, Antonio C. [1] ; Barbosa-Sampaio, Helena C. [1]
Total Authors: 8
[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Struct & Funct Biol, POB 6109, BR-13083865 Campinas, SP - Brazil
[2] Univ Estadual Campinas, UNICAMP, HEMOCTR, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Cellular Physiology; v. 233, n. 9, p. 7112-7119, SEP 2018.
Web of Science Citations: 4

GTPase activating proteins (GAPs) are ubiquitously expressed, and their role in cellular adhesion and membrane traffic processes have been well described. TBC1D1, which is a Rab-GAP, is necessary for adequate glucose uptake by muscle cells, whereas increased TCGAP, which is a Rho-GAP, decreases GLUT4 translocation, and consequently glucose uptake in adipocytes. Here, we assessed the possible involvement of ARHGAP21, a Rho-GAP protein, in glucose homeostasis. For this purpose, wild type mice and ARHGAP21 transgenic whole-body gene-deficiency mice (heterozygous mice, expressing approximately 50% of ARHGAP21) were fed either chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD). Het-HFD mice showed a reduction in white fat storage, reflected in a lower body weight gain. These mice also displayed an improvement in insulin sensitivity and glucose tolerance, which likely contributed to reduced insulin secretion and pancreatic beta cell area. The reduction of body weight was also observed in Het mice and this phenomenon was associated with an increase in brown adipose tissue and reduced muscle weight, without alteration in glucose-insulin homeostasis. In conclusion, the whole body ARHGAP21 reduction improved glucose homeostasis and protected against diet-induced obesity specifically in Het-HFD mice. However, the mechanism by which ARHGAP21 leads to these outcomes requires further investigation. (AU)

FAPESP's process: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass
Grantee:Antonio Carlos Boschiero
Support type: Research Projects - Thematic Grants
FAPESP's process: 12/14993-9 - Type 3 muscarinic receptor activation and association with ADP-rybosilation factor 1 and 6 on the pancreatic beta-cell function: downstream signalling pathways, islet arquitecture and insulin secretion
Grantee:Helena Cristina de Lima Barbosa Sampaio
Support type: Research Grants - Young Investigators Grants