ArticleDiabetologia2010
Voltage-dependent K(+) channels are positive regulators of alpha cell action potential generation and glucagon secretion in mice and humans.
Article in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Paracrine inhibition via G protein inwardly rectifying potassium channels regulates glucagon secretion from human pancreatic alpha cells.Cell reports · 2026Article
- Review
- α-cell electrophysiology and the regulation of glucagon secretion.The Journal of endocrinology · 2023Review
- Metabolic Messengers: glucagon.Nature metabolism · 2023Review
- Regulation of α-cell glucagon secretion: The role of second messengers.Chronic diseases and translational medicine · 2022Review
- Intercellular Communication in the Islet of Langerhans in Health and Disease.Comprehensive Physiology · 2021Article
- The Glucagon-Like Adipokinetic Hormone inFrontiers in physiology · 2021Review
- Lactate activation of α-cell KMolecular metabolism · 2020Article
- 'Resistance is futile?' - paradoxical inhibitory effects of KThe Journal of physiology · 2020Review
- Glucose-mediated inhibition of calcium-activated potassium channels limits α-cell calcium influx and glucagon secretion.American journal of physiology. Endocrinology and metabolism · 2019Article
- GLP-1 suppresses glucagon secretion in human pancreatic alpha-cells by inhibition of P/Q-type CaPhysiological reports · 2018Article
- Loss of mTORC1 signaling alters pancreatic α cell mass and impairs glucagon secretion.The Journal of clinical investigation · 2017Article
- HERG Protein Plays a Role in Moxifloxacin-Induced Hypoglycemia.Journal of diabetes research · 2016Article
- Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells.The Journal of clinical investigation · 2015Article
- LKB1 couples glucose metabolism to insulin secretion in mice.Diabetologia · 2015Article
- TASK-1 Potassium Channels Limit Pancreatic α-Cell Calcium Influx and Glucagon Secretion.Molecular endocrinology (Baltimore, Md.) · 2015Article
- SUMO1 enhances cAMP-dependent exocytosis and glucagon secretion from pancreatic α-cells.The Journal of physiology · 2014Article
- ATP-regulated potassium channels and voltage-gated calcium channels in pancreatic alpha and beta cells: similar functions but reciprocal effects on secretion.Diabetologia · 2014Review
- Article
- The functional and molecular characterisation of human embryonic stem cell-derived insulin-positive cells compared with adult pancreatic beta cells.Diabetologia · 2012Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe regulation of glucagon secretion from alpha cells is poorly understood. Since action potential firing at low glucose is required for glucagon secretion, we hypothesised that voltage-dependent K(+) (Kv) currents limit glucagon secretion under these conditions, similarly to their role in insulin secretion.
methodsKv currents and action potential firing of mouse and human alpha cells, identified by immunostaining, were examined by whole-cell patch-clamp. Glucagon secretion from mouse and human islets was measured by ELISA.
resultsKv current density was 35% larger in alpha than in beta cells. Alpha cell Kv channels were sensitive to block by tetraethylammonium (TEA) and 4-aminopyridine. Surprisingly, Kv channel inhibition reduced glucagon release to the same extent as glucose. Robust action potential firing was observed in beta cells when ATP-sensitive K(+) channels were closed, but in alpha cells a negative current (-8 pA) injection was required for action potential firing. TEA (0.5 mmol/l) impaired alpha cell action potential firing, which could be restored by further hyperpolarising current injection (-16 pA). Kv currents were more sensitive to the Kv2 inhibitor stromatoxin (100 nmol/l) in mouse (80%) than in human (45%) alpha cells. Finally, the maxi-K (BK) channel inhibitor iberiotoxin (100 nmol/l) blocked 55% of the current in human alpha cells and inhibited glucagon release from human islets. CONCLUSIONS/
interpretationKv currents in alpha cells are positive regulators of glucagon secretion. These currents, mediated by Kv2 and BK channels, limit membrane depolarisation, and prevent inactivation of alpha cell action potentials and suppression of glucagon release.
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