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

Ferreira, Sandra Mara; Costa-Júnior, José Maria; Kurauti, Mirian Ayumi; Leite, Nayara C.; Ortis, Fernanda; Rezende, Luiz F.; Barbosa, Helena C.; Boschero, Antônio Carlos; Santos, Gustavo Jorge dos

doi:10.3389/fendo.2020.599165

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…This effect was also observed in 18-month-old rats ( Supplementary Figure S3 ) and this may be involved with an impaired glucose homeostasis, frequently observed in aged subjects. Previously, we suggested that an increased expression of the inducible nitric oxide synthase (iNOS), observed in the liver from 10-month-old mice, should be linked to the reduction in the hepatic IDE activity, because it was reported that nitric oxide (NO) inhibits insulin degradation by IDE ( 40 , 41 ). Here, the expression of iNOS was not increased, in fact, it was decreased in the liver from 18-month-old mice compared with controls ( Supplementary Figure S4 ), suggesting that other molecular mechanisms must be involved in the impairment on IDE function in the liver of these OLD mice ( 35 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

Aging Reduces Insulin Clearance in Mice

et al. 2021

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Hyperinsulinemia is frequently associated with aging and may cause insulin resistance in elderly. Since insulin secretion and clearance decline with age, hyperinsulinemia seems to be maintained, primarily, due to a decrease in the insulin clearance. To investigate these aging effects, 3- and 18-month-old male C57BL/6 mice were subjected to intraperitoneal glucose and insulin tolerance tests (ipGTT and ipITT) and, during the ipGTT, plasma c-peptide and insulin were measure to evaluate in vivo insulin clearance. Glucose-stimulated insulin secretion in isolated pancreatic islets was also assessed, and liver samples were collected for molecular analyses (western blot). Although insulin sensitivity was not altered in the old mice, glucose tolerance, paradoxically, seems to be increased, accompanied by higher plasma insulin, during ipGTT. While insulin secretion did not increase, insulin clearance was reduced in the old mice, as suggested by the lower c-peptide:insulin ratio, observed during ipGTT. Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) and insulin-degrading enzyme (IDE), as well as the activity of this enzyme, were reduced in the liver of old mice, justifying the decreased insulin clearance observed in these mice. Therefore, loss of hepatic CEACAM1 and IDE function may be directly related to the decline in insulin clearance during aging.

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Section: Discussionmentioning

confidence: 99%

Aging Reduces Insulin Clearance in Mice

et al. 2021

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“…Interestingly, Arhgap21 has been suggested as a key regulator in various cellular pathways [ 122 ]. It was shown that ARHGAP21 had an inhibitory role during insulin secretion via glucose stimulation [ 123 ]. Since RP23-177L19.1 was also changed by the IGF-1 treatments in our study ( Figure 4 C) and other studies have shown that there is a regulatory relationship between protein-coding genes and lncRNA when they share the promoter sequence, it could be expected that there is also an association between Arhgap21 and this lncRNA.…”

Section: Discussionmentioning

confidence: 99%

Identification of IGF-1 Effects on White Adipose Tissue and Hippocampus in Alzheimer’s Disease Mice via Transcriptomic and Cellular Analysis

Kim,

Jo,

Arjunan

et al. 2024

IJMS

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Alzheimer’s disease (AD) stands as the most prevalent neurodegenerative disorder, characterized by a multitude of pathological manifestations, prominently marked by the aggregation of amyloid beta. Recent investigations have revealed a compelling association between excessive adiposity and glial activation, further correlating with cognitive impairments. Additionally, alterations in levels of insulin-like growth factor 1 (IGF-1) have been reported in individuals with metabolic conditions accompanied by memory dysfunction. Hence, our research endeavors to comprehensively explore the impact of IGF-1 on the hippocampus and adipose tissue in the context of Alzheimer’s disease. To address this, we have conducted an in-depth analysis utilizing APP/PS2 transgenic mice, recognized as a well-established mouse model for Alzheimer’s disease. Upon administering IGF-1 injections to the APP/PS2 mice, we observed notable alterations in their behavioral patterns, prompting us to undertake a comprehensive transcriptomic analysis of both the hippocampal and adipose tissues. Our data unveiled significant modifications in the functional profiles of these tissues. Specifically, in the hippocampus, we identified changes associated with synaptic activity and neuroinflammation. Concurrently, the adipose tissue displayed shifts in processes related to fat browning and cell death signaling. In addition to these findings, our analysis enabled the identification of a collection of long non-coding RNAs and circular RNAs that exhibited significant changes in expression subsequent to the administration of IGF-1 injections. Furthermore, we endeavored to predict the potential roles of these identified RNA molecules within the context of our study. In summary, our study offers valuable transcriptome data for hippocampal and adipose tissues within an Alzheimer’s disease model and posits a significant role for IGF-1 within both the hippocampus and adipose tissue.

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