ArticleThe Journal of biological chemistry2013
Leptin regulates KATP channel trafficking in pancreatic β-cells by a signaling mechanism involving AMP-activated protein kinase (AMPK) and cAMP-dependent protein kinase (PKA).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 75 citations in OpenAlex.
- Ion channels and actin: A tale of two friends.Histology and histopathology · 2025Review
- Systemic Glucose Homeostasis Requires Pancreatic but Not Neuronal ATP-sensitive Potassium Channels.Function (Oxford, England) · 2025Article
- Review
- Article
- The Interplay of Adipokines and Pancreatic Beta Cells in Metabolic Regulation and Diabetes.Biomedicines · 2023Review
- Antipsychotics impair regulation of glucose metabolism by central glucose.Molecular psychiatry · 2022Article
- Similarities in Calcium Oscillations Between Neonatal Mouse Islets and Mature Islets Exposed to Chronic Hyperglycemia.Endocrinology · 2022Article
- Subcellular trafficking and endocytic recycling of KAmerican journal of physiology. Cell physiology · 2022Review
- Role of upregulation of the KAging cell · 2022Article
- Interorgan crosstalk in pancreatic islet function and pathology.FEBS letters · 2022Review
- ATP-Sensitive Potassium Channels in Hyperinsulinism and Type 2 Diabetes: Inconvenient Paradox or New Paradigm?Diabetes · 2022Review
- Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells.Biomolecules · 2022Review
- Gallbladder Cancer Cell-Derived Exosome-Mediated Transfer of Leptin Promotes Cell Invasion and Migration by Modulating STAT3-Mediated M2 Macrophage Polarization.Analytical cellular pathology (Amsterdam) · 2022Article
- Channeling β-cell Maturity: KATP Surface Localization Imparts Glucose Sensing.Endocrinology · 2021Article
- Beta-Cell Ion Channels and Their Role in Regulating Insulin Secretion.Comprehensive Physiology · 2021Review
- Decreased KATP Channel Activity Contributes to the Low Glucose Threshold for Insulin Secretion of Rat Neonatal Islets.Endocrinology · 2021Article
- Neuromedin B receptor stimulation of Cav3.2 T-type CaTheranostics · 2021Article
- Leptin modulates pancreatic β-cell membrane potential through Src kinase-mediated phosphorylation of NMDA receptors.The Journal of biological chemistry · 2020Article
- Radix Polygoni Multiflori and Its Main Component Emodin Attenuate Non-Alcoholic Fatty Liver Disease in Zebrafish by Regulation of AMPK Signaling Pathway.Drug design, development and therapy · 2020Article
- AMP-activated protein kinase slows D2 dopamine autoreceptor desensitization in substantia nigra neurons.Neuropharmacology · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Pancreatic β-cells secrete insulin in response to metabolic and hormonal signals to maintain glucose homeostasis. Insulin secretion is under the control of ATP-sensitive potassium (KATP) channels that play key roles in setting β-cell membrane potential. Leptin, a hormone secreted by adipocytes, inhibits insulin secretion by increasing KATP channel conductance in β-cells. We investigated the mechanism by which leptin increases KATP channel conductance. We show that leptin causes a transient increase in surface expression of KATP channels without affecting channel gating properties. This increase results primarily from increased channel trafficking to the plasma membrane rather than reduced endocytosis of surface channels. The effect of leptin on KATP channels is dependent on the protein kinases AMP-activated protein kinase (AMPK) and PKA. Activation of AMPK or PKA mimics and inhibition of AMPK or PKA abrogates the effect of leptin. Leptin activates AMPK directly by increasing AMPK phosphorylation at threonine 172. Activation of PKA leads to increased channel surface expression even in the presence of AMPK inhibitors, suggesting AMPK lies upstream of PKA in the leptin signaling pathway. Leptin signaling also leads to F-actin depolymerization. Stabilization of F-actin pharmacologically occludes, whereas destabilization of F-actin simulates, the effect of leptin on KATP channel trafficking, indicating that leptin-induced actin reorganization underlies enhanced channel trafficking to the plasma membrane. Our study uncovers the signaling and cellular mechanism by which leptin regulates KATP channel trafficking to modulate β-cell function and insulin secretion.
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Registered trials
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