ArticleDiabetologia2004
Antidiabetic effect of novel modulating peptides of G-protein-coupled kinase in experimental models of diabetes.
Article in Diabetologia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 52 citations in OpenAlex.
- Recent advances in the development of GRK2 inhibitors: blocking the interaction of GRK2 with its partners.Acta pharmacologica Sinica · 2026Review
- A New Concept in Antidiabetic Therapeutics: A Concerted Removal of Labile Iron and Intracellular Deposition of Zinc.Diabetes & metabolism journal · 2024Article
- Characterizing Adrenergic Regulation of Glucose Transporter 4-Mediated Glucose Uptake and Metabolism in the Heart.JACC. Basic to translational science · 2023Article
- GRK2 levels in myeloid cells modulate adipose-liver crosstalk in high fat diet-induced obesity.Cellular and molecular life sciences : CMLS · 2020Article
- Myeloid GRK2 Regulates Obesity-Induced Endothelial Dysfunction by Modulating Inflammatory Responses in Perivascular Adipose Tissue.Antioxidants (Basel, Switzerland) · 2020Article
- Article
- Antidiabetic and Cardioprotective Effects of Pharmacological Inhibition of GRK2 in db/db Mice.International journal of molecular sciences · 2019Article
- G Protein-Coupled Receptor Kinase 2 (GRK2) as a Potential Therapeutic Target in Cardiovascular and Metabolic Diseases.Frontiers in pharmacology · 2019Review
- Therapeutic Targets for Treatment of Heart Failure: Focus on GRKs and β-Arrestins Affecting βAR Signaling.Frontiers in pharmacology · 2018Review
- Suppression of GRK2 expression reduces endothelial dysfunction by restoring glucose homeostasis.Scientific reports · 2017Article
- β-Adrenergic Receptor and Insulin Resistance in the Heart.Biomolecules & therapeutics · 2017Review
- "Freeze, Don't Move": How to Arrest a Suspect in Heart Failure - A Review on Available GRK2 Inhibitors.Frontiers in cardiovascular medicine · 2016Review
- Reversal of diet-induced obesity and insulin resistance by inducible genetic ablation of GRK2.Science signaling · 2015Article
- G-protein-coupled receptor kinase 2 and endothelial dysfunction: molecular insights and pathophysiological mechanisms.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2015Review
- Identification and characterization of amlexanox as a G protein-coupled receptor kinase 5 inhibitor.Molecules (Basel, Switzerland) · 2014Article
- Trafficking GRK2: Cellular and Metabolic consequences of GRK2 subcellular localization.Translational medicine @ UniSa · 2014Review
- G protein-coupled receptor kinase 2: a link between myocardial contractile function and cardiac metabolism.Circulation research · 2014Review
- Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2.Diabetologia · 2012Review
- Dual mode of glucagon receptor internalization: role of PKCα, GRKs and β-arrestins.Experimental cell research · 2011Article
- G protein coupled receptor kinases as therapeutic targets in cardiovascular disease.Circulation research · 2011Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisG-protein-coupled receptor kinases (GRKs) play a key role in agonist-induced desensitisation of G-protein-coupled receptors (GPCRs) that are involved in metabolic regulation and glucose homeostasis. Our aim was to examine whether small peptides derived from the catalytic domain of GRK2 and -3 would ameliorate Type 2 diabetes in three separate animal models of diabetes.
methodsSynthetic peptides derived from a kinase-substrate interaction site in GRK2/3 were initially screened for their effect on in vitro melanogenesis, a GRK-mediated process. The most effective peptides were administered intraperitoneally, utilising a variety of dosing regimens, to Psammomys obesus gerbils, Zucker diabetic fatty (ZDF) rats, or db/db mice. The metabolic effects of these peptides were assessed by measuring fasting and fed blood glucose levels and glucose tolerance.
resultsTwo peptides, KRX-683(107) and KRX-683(124), significantly reduced fed-state blood glucose levels in the diabetic Psammomys obesus. In animals treated with KRX-683(124) at a dose of 12.5 mg/kg weekly for 7 weeks, ten of eleven treated animals responded with mean blood glucose significantly lower than controls (4.7+/-0.4 vs 16.8+/-0.8 mmol/l, p</=0.0001). Significant reductions in blood glucose compared with controls were also seen in ZDF rats administered KRX-683(124) and in db/db mice, which had significantly reduced fasting and 2-hour postprandial glucose levels after the treatment. CONCLUSIONS/
interpretationSequence-based peptides derived from GRK2/3 have an antidiabetic effect demonstrated in three different animal models of Type 2 diabetes. By modulating GRK2/3 activity, these peptides enhance GPCR-initiated signal transduction, resulting in improved glucose homeostasis. Sequence-based peptide modulation of GRK could prove useful in the 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.