ArticleBritish journal of pharmacology2010
Phosphatidylinositol 3-kinase-δ up-regulates L-type Ca2+ currents and increases vascular contractility in a mouse model of type 1 diabetes.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 40 citations in OpenAlex.
- Environmental pollutants and phosphoinositide signaling in autoimmunity.Journal of hazardous materials · 2024Review
- Insulin and aging - a disappointing relationship.Frontiers in endocrinology · 2023Review
- Mechanisms of Vascular CaHandbook of experimental pharmacology · 2023Article
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
- Gene Expression Signatures Reveal Common Virus Infection Pathways in Target Tissues of Type 1 Diabetes, Hashimoto's Thyroiditis, and Celiac Disease.Frontiers in immunology · 2022Article
- Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle.Cellular and molecular life sciences : CMLS · 2021Review
- Insulin: too much of a good thing is bad.BMC medicine · 2020Review
- Role of Phosphatidylinositol 3-Kinase (PI3K), Mitogen-Activated Protein Kinase (MAPK), and Protein Kinase C (PKC) in Calcium Signaling Pathways Linked to the αFrontiers in physiology · 2019Article
- Inhibition of p110δ PI3K prevents inflammatory response and restenosis after artery injury.Bioscience reports · 2017Article
- Rho-kinase and the nitric oxide pathway modulate basilar arterial reactivity to acetylcholine and angiotensin II in streptozotocin-induced diabetic mice.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Salidroside contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic Goto-Kakizaki Rats by inhibition of L-type calcium channel in smooth muscle cells.BMC pharmacology & toxicology · 2017Article
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- Diabetes-induced oxidative stress mediates upregulation of RhoA/Rho kinase pathway and hypercontractility of gastric smooth muscle.PloS one · 2017Article
- Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca²⁺ handling in smooth muscle cells.Cardiovascular diabetology · 2016Article
- Effects of streptozotocin and unilateral nephrectomy on L-type Ca²⁺ channels and membrane capacitance in arteriolar smooth muscle cells.Pflugers Archiv : European journal of physiology · 2015Article
- DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13½ years: Project Ice Storm.Epigenetics · 2015Article
- Mural propagation of descending vasa recta responses to mechanical stimulation.American journal of physiology. Renal physiology · 2013Article
- Functional characterization of voltage-dependent Ca(2+) channels in mouse pulmonary arterial smooth muscle cells: divergent effect of ROS.American journal of physiology. Cell physiology · 2013Article
- Isoform-selective induction of human p110δ PI3K expression by TNFα: identification of a new and inducible PIK3CD promoter.The Biochemical journal · 2012Article
- Tuning in to the ‘right’ calcium channel regulation in experimental models of diabetes.British journal of pharmacology · 2010Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeVasculopathies represent the main cause of morbidity and mortality in diabetes. Vascular malfunctioning in diabetes is associated with abnormal vasoconstriction and Ca(2+) handling by smooth muscle cells (SMC). Phosphatidylinositol 3-kinases (PI3K) are key mediators of insulin action and have been shown to modulate the function of voltage-dependent L-type Ca(2+) channels (Ca(V) 1.2). In the present work, we investigated the involvement of PI3K signalling in regulating Ca(2+) current through Ca(V) 1.2 (I(Ca,L) ) and vascular dysfunction in a mouse model of type I diabetes. EXPERIMENTAL APPROACH: Changes in isometric tension were recorded on myograph. Ca(2+) currents in freshly dissociated mice aortic SMCs were measured using the whole-cell patch-clamp technique. Antisense techniques were used to knock-down the PI3Kδ isoform. KEY RESULTS Contractile responses to phenylephrine and KCl were strongly enhanced in diabetic aorta independent of a functional endothelium. The magnitude of phenylephrine-induced I(Ca,L) was also greatly augmented. PI3Kδ expression, but not PI3Kα, PI3Kβ, PI3Kγ, was increased in diabetic aortas and treatment of vessels with a selective PI3Kδ inhibitor normalized I(Ca,L) and contractile response of diabetic vessels. Moreover, knock-down of PI3Kδin vivo decreased PI3Kδ expression and normalized I(Ca,L) and contractile response of diabetic vessels ex vivo. CONCLUSIONS AND IMPLICATIONS: Phosphatidylinositol 3-kinase δ was essential to the increased vascular contractile response in our model of type I diabetes. PI3Kδ signalling was up-regulated and most likely accounted for the increased I(Ca,L,) leading to increased vascular contractility. Blockade of PI3Kδ may represent a novel therapeutic approach to treat vascular dysfunction in diabetic patients.
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