Targeting Small GTPases and Their Prenylation in Diabetes Mellitus
Open accessAbstract
A fundamental role of pancreatic β-cells to maintain proper blood glucose level is controlled by the Ras superfamily of small GTPases that undergo post-translational modifications, including prenylation. This covalent attachment with either a farnesyl or a geranylgeranyl group controls their localization, activity, and protein-protein interactions. Small GTPases are critical in maintaining glucose homeostasis acting in the pancreas and metabolically active tissues such as skeletal muscles, liver, or adipocytes. Hyperglycemia-induced upregulation of small GTPases suggests that inhibition of these pathways deserves to be considered as a potential therapeutic approach in treating T2D. This Perspective presents how inhibition of various points in the mevalonate pathway might affect protein prenylation and functioning of diabetes-affected tissues and contribute to chronic inflammation involved in diabetes mellitus (T2D) development. We also demonstrate the currently available molecular tools to decipher the mechanisms linking the mevalonate pathway's enzymes and GTPases with diabetes.
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Small GTPases need post-translational modification to target them to cellular membranes and be active.
“All these small GTPase need post-translational modification to target them to cellular membranes and be active [16,17].”
From Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome (2022) · cites this paper as [17]
The Overview of Superfamily of Small GTPases and Enzymes within the Mevalonate Pathway (page unavailable) says small GTPases usually carry a post-translationally attached prenyl tail and explains that masking this tail prevents Rho and Rab from associating with target membranes. It does not establish that all small GTPases require modification to become active; it describes activation as the exchange of GDP for GTP. (LLM, conf=0.87)
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Flagged first, then by citations
Research works printed but not linked: 1
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Cited by
Sorted by citations
Brain Cholesterol Biosynthetic Pathway Is Altered in a Preclinical Model of Fragile X Syndrome
Parente, M., Tonini, C., Buzzelli, V., Carbone, E., Trezza, V., & Pallottini, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063408 · Cited by 11 · see citing works
“All these small GTPase need posttranslational modification to target them to cellular membranes and be active [16,17].”
Background
- Authors
- Gendaszewska-Darmach, E., Garstka, M. A., & Błażewska, K. M.
- Affiliations
- Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego Street 4/10, 90-924 Łódź, Poland
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Lodz University of Technology (PL)
- Corresponding author
- Garstka, Malgorzata A.
- Błażewska, Katarzyna M.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-07-08
- Volume
- 64
- Issue
- 14
- Pages
- 9677-9710
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- PMC
- PMC8389838
- OpenAlex
- W3181493345
- Cited by
- 35
- References
- 301
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 12 · 2021: 2
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Medicinal Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Narodowe Centrum Nauki (2014/14/E/ST5/00491, 2018/31/B/NZ9/02433)
- Second Affiliated Hospital, Xiâ??an Jiaotong University (82668330, 82668428)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- small GTPases, Ras superfamily, protein prenylation, farnesyltransferase, geranylgeranyltransferase, mevalonate pathway, type 2 diabetes, pancreatic beta cells, glucose homeostasis, hyperglycemia, chronic inflammation, GTPase inhibitors, therapeutic target
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Enzyme Inhibitors, Humans, Hypoglycemic Agents, Structure-Activity Relationship, Molecular Structure, Monomeric GTP-Binding Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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