ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2016
Metabolic Stress Induces Caspase-3 Mediated Degradation and Inactivation of Farnesyl and Geranylgeranyl Transferase Activities in Pancreatic β-Cells.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 32 citations in OpenAlex.
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- Protein prenylation in islet β-cell function in health and metabolic stress.Biochemical pharmacology · 2025Review
- The RhoGDIβ-Rac1-CARD9 Signaling Module Mediates Islet β-Cell Dysfunction Under Chronic Hyperglycemia.Cells · 2025Review
- Novel Roles for Geranylgeranyl Transferase-III (GGTase-III) in Insulin Secretion.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2025Article
- Mechanistic Insights IntoDiabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Protective Effects of Sitagliptin on Streptozotocin-Induced Hepatic Injury in Diabetic Rats: A Possible Mechanisms.Diseases (Basel, Switzerland) · 2023Article
- Alpha4 contributes to the dysfunction of the pancreatic beta cell under metabolic stress.Molecular and cellular endocrinology · 2022Article
- CARD9 Mediates Pancreatic Islet Beta-Cell Dysfunction Under the Duress of Hyperglycemic Stress.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2022Article
- Underappreciated roles for Rho GDP dissociation inhibitors (RhoGDIs) in cell function: Lessons learned from the pancreatic islet β-cell.Biochemical pharmacology · 2022Review
- Gut Metabolite Trimethylamine N-Oxide Protects INS-1 β-Cell and Rat Islet Function under Diabetic Glucolipotoxic Conditions.Biomolecules · 2021Article
- Hyperglycaemia-associated Caspase-3 predicts diabetes and coronary artery disease events.Journal of internal medicine · 2021Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Impairing committed cholesterol biosynthesis in white matter astrocytes, but not grey matter astrocytes, enhances in vitro myelination.Journal of neurochemistry · 2021Article
- Lipotoxic Impairment of Mitochondrial Function in β-Cells: A Review.Antioxidants (Basel, Switzerland) · 2021Review
- Macroglial diversity: white and grey areas and relevance to remyelination.Cellular and molecular life sciences : CMLS · 2021Review
- P-Rex1 Mediates Glucose-Stimulated Rac1 Activation and Insulin Secretion in Pancreatic β-Cells.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2020Article
- Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns.Metabolites · 2020Review
- Caspase-10 inhibits ATP-citrate lyase-mediated metabolic and epigenetic reprogramming to suppress tumorigenesis.Nature communications · 2019Article
- The Evolution of Cholesterol-Rich Membrane in Oxygen Adaption: The Respiratory System as a Model.Frontiers in physiology · 2019Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
BACKGROUND/
aimsAt least 300 prenylated proteins are identified in the human genome; the majority of which partake in a variety of cellular processes including growth, differentiation, cytoskeletal organization/dynamics and vesicle trafficking. Aberrant prenylation of proteins is implicated in human pathologies including cancer; neurodegenerative diseases, retinitis pigmentosa, and premature ageing syndromes. Original observations from our laboratory have demonstrated that prenylation of proteins [small G-proteins and γ-subunits of trimeric G-proteins] is requisite for physiological insulin secretion. Herein, we assessed the impact of metabolic stress [gluco-, lipotoxicity and ER-stress] on the functional status of protein prenylation pathway in pancreatic β-cells.
methodsFarnesyltransferase [FTase] and geranylgeranyltransferase [GGTase] activities were quantified by radioisotopic methods. Caspase-3 activation and FTase/GGTase-α subunit degradation were determined by Western blotting.
resultsWe observed that metabolic stress activates caspase-3 and induces degradation of the common α-subunit of FTase and GGTase-I in INS-1 832/13 cells, normal rodent islets and human islets leading to functional defects [inactivation] in FTase and GGTase activities. Caspase-3 activation and FTase/GGTase-α degradation were also seen in islets from the Zucker diabetic fatty [ZDF] rat, a model for Type 2 diabetes. Consequential to defects in FTase/GGTase-α signaling, we observed significant accumulation of unprenylated proteins [Rap1] in β-cells exposed to glucotoxic conditions. These findings were replicated in β-cells following pharmacological inhibition of generation of prenylpyrophosphate substrates [Simvastatin] or catalytic activity of prenylating enzymes [GGTI-2147].
conclusionsOur findings provide the first evidence to suggest that metabolic stress induced dysfunction of the islet β-cell may, in part, be due to defective protein prenylation signaling pathway.
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Registered trials
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