Hyperglycemic Stress Induces Expression, Degradation, and Nuclear Association of Rho GDP Dissociation Inhibitor 2 (RhoGDIβ) in Pancreatic β-Cells
Small G proteins (e.g., Rac1) play critical regulatory roles in islet β-cell function in health (physiological insulin secretion) and in metabolic stress (cell dysfunction and demise). Multiple regulatory factors for these G proteins, such as GDP dissociation inhibitors (GDIs), have been implicated...
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MDPI AG
2024-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/3/272 |
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| author | Noah Gleason Anjaneyulu Kowluru |
| author_facet | Noah Gleason Anjaneyulu Kowluru |
| author_sort | Noah Gleason |
| collection | DOAJ |
| description | Small G proteins (e.g., Rac1) play critical regulatory roles in islet β-cell function in health (physiological insulin secretion) and in metabolic stress (cell dysfunction and demise). Multiple regulatory factors for these G proteins, such as GDP dissociation inhibitors (GDIs), have been implicated in the functional regulation of these G proteins. The current set of investigations is aimed at understanding impact of chronic hyperglycemic stress on the expression and subcellular distribution of three known isoforms of RhoGDIs (RhoGDIα, RhoGDIβ, and RhoGDIγ) in insulin-secreting β-cells. The data accrued in these studies revealed that the expression of RhoGDIβ, but not RhoGDIα or RhoGDIγ, is increased in INS-1 832/13 cells, rat islets, and human islets. Hyperglycemic stress also promoted the cleavage of RhoGDIβ, leading to its translocation to the nuclear compartment. We also report that RhoGDIα, but not RhoGDIγ, is associated with the nuclear compartment. However, unlike RhoGDIβ, hyperglycemic conditions exerted no effects on RhoGDIα’s association with nuclear fraction. Based on these observations, and our earlier findings of the translocation of Rac1 to the nuclear compartment under the duress of metabolic stress, we conclude that the RhoGDIβ-Rac1 signaling module promotes signals from the cytosolic to the nucleus, culminating in accelerated β-cell dysfunction under metabolic stress. |
| first_indexed | 2024-03-08T04:00:10Z |
| format | Article |
| id | doaj.art-f8e0a0f14cda46a98846e02394028354 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T04:00:10Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f8e0a0f14cda46a98846e023940283542024-02-09T15:09:50ZengMDPI AGCells2073-44092024-02-0113327210.3390/cells13030272Hyperglycemic Stress Induces Expression, Degradation, and Nuclear Association of Rho GDP Dissociation Inhibitor 2 (RhoGDIβ) in Pancreatic β-CellsNoah Gleason0Anjaneyulu Kowluru1Research Service, John D. Dingell VA Medical Center, Detroit, MI 48201, USAResearch Service, John D. Dingell VA Medical Center, Detroit, MI 48201, USASmall G proteins (e.g., Rac1) play critical regulatory roles in islet β-cell function in health (physiological insulin secretion) and in metabolic stress (cell dysfunction and demise). Multiple regulatory factors for these G proteins, such as GDP dissociation inhibitors (GDIs), have been implicated in the functional regulation of these G proteins. The current set of investigations is aimed at understanding impact of chronic hyperglycemic stress on the expression and subcellular distribution of three known isoforms of RhoGDIs (RhoGDIα, RhoGDIβ, and RhoGDIγ) in insulin-secreting β-cells. The data accrued in these studies revealed that the expression of RhoGDIβ, but not RhoGDIα or RhoGDIγ, is increased in INS-1 832/13 cells, rat islets, and human islets. Hyperglycemic stress also promoted the cleavage of RhoGDIβ, leading to its translocation to the nuclear compartment. We also report that RhoGDIα, but not RhoGDIγ, is associated with the nuclear compartment. However, unlike RhoGDIβ, hyperglycemic conditions exerted no effects on RhoGDIα’s association with nuclear fraction. Based on these observations, and our earlier findings of the translocation of Rac1 to the nuclear compartment under the duress of metabolic stress, we conclude that the RhoGDIβ-Rac1 signaling module promotes signals from the cytosolic to the nucleus, culminating in accelerated β-cell dysfunction under metabolic stress.https://www.mdpi.com/2073-4409/13/3/272RhoGDIβsmall G proteinsinsulin secretionislet β-cell |
| spellingShingle | Noah Gleason Anjaneyulu Kowluru Hyperglycemic Stress Induces Expression, Degradation, and Nuclear Association of Rho GDP Dissociation Inhibitor 2 (RhoGDIβ) in Pancreatic β-Cells Cells RhoGDIβ small G proteins insulin secretion islet β-cell |
| title | Hyperglycemic Stress Induces Expression, Degradation, and Nuclear Association of Rho GDP Dissociation Inhibitor 2 (RhoGDIβ) in Pancreatic β-Cells |
| title_full | Hyperglycemic Stress Induces Expression, Degradation, and Nuclear Association of Rho GDP Dissociation Inhibitor 2 (RhoGDIβ) in Pancreatic β-Cells |
| title_fullStr | Hyperglycemic Stress Induces Expression, Degradation, and Nuclear Association of Rho GDP Dissociation Inhibitor 2 (RhoGDIβ) in Pancreatic β-Cells |
| title_full_unstemmed | Hyperglycemic Stress Induces Expression, Degradation, and Nuclear Association of Rho GDP Dissociation Inhibitor 2 (RhoGDIβ) in Pancreatic β-Cells |
| title_short | Hyperglycemic Stress Induces Expression, Degradation, and Nuclear Association of Rho GDP Dissociation Inhibitor 2 (RhoGDIβ) in Pancreatic β-Cells |
| title_sort | hyperglycemic stress induces expression degradation and nuclear association of rho gdp dissociation inhibitor 2 rhogdiβ in pancreatic β cells |
| topic | RhoGDIβ small G proteins insulin secretion islet β-cell |
| url | https://www.mdpi.com/2073-4409/13/3/272 |
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