Role of High Voltage-Gated Ca 2+ Channel Subunits in Pancreatic β-Cell Insulin Release. From Structure to Function

The pancreatic islets of Langerhans secrete several hormones critical for glucose homeostasis. The β-cells, the major cellular component of the pancreatic islets, secrete insulin, the only hormone capable of lowering the plasma glucose concentration. The counter-regulatory hormone glucagon is secret...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2021-08, Vol.10 (8)
Main Authors: Tuluc, Petronel, Theiner, Tamara, Jacobo-Piqueras, Noelia, Geisler, Stefanie M
Format: Article
Language:English
Subjects:
Animals
Blood Glucose - metabolism
Calcium Channels - genetics
Calcium Channels - metabolism
Calcium Signaling
Diabetes Mellitus - blood
Diabetes Mellitus - genetics
Diabetes Mellitus - metabolism
Diabetes Mellitus - pathology
Exocytosis
Humans
Insulin - metabolism
Insulin-Secreting Cells - metabolism
Insulin-Secreting Cells - pathology
Ion Channel Gating
Membrane Potentials
Secretory Pathway
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Summary:The pancreatic islets of Langerhans secrete several hormones critical for glucose homeostasis. The β-cells, the major cellular component of the pancreatic islets, secrete insulin, the only hormone capable of lowering the plasma glucose concentration. The counter-regulatory hormone glucagon is secreted by the α-cells while δ-cells secrete somatostatin that via paracrine mechanisms regulates the α- and β-cell activity. These three peptide hormones are packed into secretory granules that are released through exocytosis following a local increase in intracellular Ca concentration. The high voltage-gated Ca channels (HVCCs) occupy a central role in pancreatic hormone release both as a source of Ca required for excitation-secretion coupling as well as a scaffold for the release machinery. HVCCs are multi-protein complexes composed of the main pore-forming transmembrane α and the auxiliary intracellular β, extracellular α δ, and transmembrane γ subunits. Here, we review the current understanding regarding the role of all HVCC subunits expressed in pancreatic β-cell on electrical activity, excitation-secretion coupling, and β-cell mass. The evidence we review was obtained from many seminal studies employing pharmacological approaches as well as genetically modified mouse models. The significance for diabetes in humans is discussed in the context of genetic variations in the genes encoding for the HVCC subunits.
ISSN:2073-4409