ArticleAmerican journal of physiology. Endocrinology and metabolism2012
SUMO downregulates GLP-1-stimulated cAMP generation and insulin secretion.
Article in American journal of physiology. Endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- Signaling architecture of the glucagon-like peptide-1 receptor.The Journal of clinical investigation · 2026Review
- Emerging Roles of Post-Translational Modifications in Metabolic Homeostasis and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Post-Translational Modifications and Diabetes.Biomolecules · 2024Review
- Exploring potential targets for natural product therapy of DN: the role of SUMOylation.Frontiers in pharmacology · 2024Review
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- Posttranslational modifications in diabetes: Mechanisms and functions.Reviews in endocrine & metabolic disorders · 2022Review
- β-Cell Knockout of SENP1 Reduces Responses to Incretins and Worsens Oral Glucose Tolerance in High-Fat Diet-Fed Mice.Diabetes · 2021Article
- Mechanisms controlling pancreatic islet cell function in insulin secretion.Nature reviews. Molecular cell biology · 2021Review
- Muscle RING-finger protein-1 (MuRF1) functions and cellular localization are regulated by SUMO1 post-translational modification.Journal of molecular cell biology · 2019Article
- Protein SUMOylation regulates insulin secretion at multiple stages.Scientific reports · 2019Article
- Both conditional ablation and overexpression of E2 SUMO-conjugating enzyme (UBC9) in mouse pancreatic beta cells result in impaired beta cell function.Diabetologia · 2018Article
- A post-translational balancing act: the good and the bad of SUMOylation in pancreatic islets.Diabetologia · 2018Article
- Article
- Glucagon-Like Peptide-1 and Its Class B G Protein-Coupled Receptors: A Long March to Therapeutic Successes.Pharmacological reviews · 2016Review
- Pancreatic Beta Cell G-Protein Coupled Receptors and Second Messenger Interactions: A Systems Biology Computational Analysis.PloS one · 2016Article
- Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells.The Journal of clinical investigation · 2015Article
- Regulation of translesion DNA synthesis: Posttranslational modification of lysine residues in key proteins.DNA repair · 2015Review
- Chronic hyperglycemia downregulates GLP-1 receptor signaling in pancreatic β-cells via protein kinase A.Molecular metabolism · 2015Article
- Autophagy deficiency in β cells blunts incretin-induced suppression of glucagon release from α cells.Islets · 2015Article
- SUMOylation protects against IL-1β-induced apoptosis in INS-1 832/13 cells and human islets.American journal of physiology. Endocrinology and metabolism · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Glucagon-like peptide-1 (GLP-1)-based incretin therapy is becoming central to the treatment of type 2 diabetes. Activation of incretin hormone receptors results in rapid elevation of cAMP followed by enhanced insulin secretion. However, the incretin effect may be significantly impaired in diabetes. The objective of this study is to investigate downregulation of GLP-1 signaling by small ubiquitin-related modifier protein (SUMO). Mouse islets exposed to high glucose showed increased expression of endogenous SUMO transcripts and its conjugating enzyme Ubc-9. Overexpression of SUMO-1 in mouse insulinoma 6 (MIN6) cells and primary mouse β-cells resulted in reduced static and real-time estimates of intracellular cAMP upon receptor stimulation with exendin-4, a GLP-1 receptor (GLP-1R) agonist. GLP1-R was covalently modified by SUMO. Overexpression of SUMO-1 attenuated cell surface trafficking of GLP-1R, which resulted in significantly reduced insulin secretion when stimulated by exendin-4. Partial knock down of SUMO-conjugating enzyme Ubc-9 resulted in enhanced exendin-4-stimulated insulin secretion in mouse islets exposed to high glucose. Thus, SUMO modification of the GLP-1R could be a contributing factor to reduced incretin responsiveness. Elucidating mechanisms of GLP-1R regulation by sumoylation will help improve our understanding of incretin biology and of GLP-1-based treatment of type 2 diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.