ArticleDiabetologia2009
Serine-385 phosphorylation of inwardly rectifying K+ channel subunit (Kir6.2) by AMP-dependent protein kinase plays a key role in rosiglitazone-induced closure of the K(ATP) channel and insulin secretion in rats.
Article in Diabetologia, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- Excess of rare noncoding variants in several type 2 diabetes candidate genes among Asian Indian families.Communications medicine · 2025Article
- Nicotinamide Mononucleotide (NMN) Ameliorates Free Fatty Acid-Induced Pancreatic β-Cell Dysfunction via the NADInternational journal of molecular sciences · 2024Article
- SubSol-HIe is an AMPK-dependent hypoxia-responsive subnucleus of the nucleus tractus solitarius that coordinates the hypoxic ventilatory response and protects against apnoea in mice.Pflugers Archiv : European journal of physiology · 2024Article
- Protein Kinases in Obesity, and the Kinase-Targeted Therapy.Advances in experimental medicine and biology · 2024Review
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life.International journal of molecular sciences · 2022Review
- Roles of AMPK and Its Downstream Signals in Pain Regulation.Life (Basel, Switzerland) · 2021Review
- Peroxisome Proliferator-Activated Receptors as Molecular Links between Caloric Restriction and Circadian Rhythm.Nutrients · 2020Review
- Review
- AMPK and the Need to Breathe and Feed: What's the Matter with Oxygen?International journal of molecular sciences · 2020Review
- The relevance of AMP-activated protein kinase in insulin-secreting β cells: a potential target for improving β cell function?Journal of physiology and biochemistry · 2019Review
- Pioglitazone Ameliorates Atorvastatin-Induced Islet Cell Dysfunction through Activation of FFA1 in INS-1 Cells.Journal of diabetes research · 2019Article
- AMP-Activated Protein Kinase (AMPK)-Dependent Regulation of Renal Transport.International journal of molecular sciences · 2018Review
- Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line.Scientific reports · 2018Article
- AMP-activated protein kinase inhibits Kv 1.5 channel currents of pulmonary arterial myocytes in response to hypoxia and inhibition of mitochondrial oxidative phosphorylation.The Journal of physiology · 2016Article
- The emerging role of AMPK in the regulation of breathing and oxygen supply.The Biochemical journal · 2016Review
- AMP kinase regulates ligand-gated K-ATP channels in substantia nigra dopamine neurons.Neuroscience · 2016Article
- Visualization of Compartmentalized Kinase Activity Dynamics Using Adaptable BimKARs.Chemistry & biology · 2015Article
- D-chiro-inositol glycan stimulates insulin secretion in pancreatic β cells.Molecular and cellular endocrinology · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisRosiglitazone, an insulin sensitiser, not only improves insulin sensitivity but also enhances insulin secretory capacity by ameliorating gluco- and lipotoxicity in beta cells. Rosiglitazone can stimulate insulin secretion at basal and high glucose levels via a phosphatidylinositol 3-kinase (PI3K)-dependent pathway. We hypothesised that regulation of phosphorylation of the ATP-sensitive potassium (K(ATP)) channel might serve as a key step in the regulation of insulin secretion.
methodsInsulin secretory responses were studied in an isolated pancreas perfusion system, cultured rat islets and MIN6 and RINm5F beta cells. Signal transduction pathways downstream of PI3K were explored to link rosiglitazone to K(ATP) channel conductance with patch clamp techniques and insulin secretion measured by ELISA.
resultsRosiglitazone stimulated AMP-activated protein kinase (AMPK) activity and induced inhibition of the K(ATP) channel conductance in islet beta cells; both effects were blocked by the PI3K inhibitor LY294002. Following stimulation of AMPK by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a pharmacological activator, both AICAR-stimulated insulin secretion and inhibition of K(ATP) channel conductance were unaffected by LY294002, indicating that AMPK activation occurs at a site downstream of PI3K activity. The serine residue at amino acid position 385 of Kir6.2 was found to be the substrate phosphorylation site of AMPK when activated by rosiglitazone or AICAR. CONCLUSIONS/
interpretationOur data indicate that PI3K-dependent activation of AMPK is required for rosiglitazone-stimulated insulin secretion in pancreatic beta cells. Phosphorylation of the Ser(385) residue of the Kir6.2 subunit of the K(ATP) channel by AMPK may play a role in insulin secretion.
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