Regulation of insulin secretion in islets of Langerhans by Ca(2+)channels.
Insulin secretion from beta-cells of the pancreatic islets of Langerhans is triggered by Ca(2+) influx through voltage-dependent Ca(2+) channels. Electrophysiological and molecular studies indicate that beta-cells express several subtypes of these channels. This review discusses their roles in regulating insulin secretion, focusing on recent studies using beta-cells, exogenous expression systems, and Ca(2+) channel knockout mice. These investigations reveal that L-type Ca(2+) channels in the beta-cell physically interact with the secretory apparatus by binding to synaptic proteins on the plasma membrane and insulin granule. As a result, Ca(2+) influx through L-type channels efficiently and rapidly stimulates release of a pool of insulin granules in close contact with the channels. Thus, L-type Ca(2+) channel activity is preferentially coupled to exocytosis in the beta-cell, and plays a critical role in regulating the dynamics of insulin secretion. Non-L-type channels carry a significant portion of the total voltage-dependent Ca(2+) current in beta-cells and cell lines from some species, but nevertheless account for only a small fraction of insulin secretion. These channels may regulate exocytosis indirectly by affecting membrane potential or second messenger signaling pathways. Finally, voltage-independent Ca(2+) entry pathways and their potential roles in beta-cell function are discussed. The emerging picture is that Ca(2+) channels regulate insulin secretion at multiple sites in the stimulus-secretion coupling pathway, with the specific role of each channel determined by its biophysical and structural properties.
Mears
David
D
Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814, USA. dmears@usuhs.mil.
D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D005089:Exocytosis / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D015640:Ion Channel Gating / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
D020746:Calcium Channels, L-Type; D007328:Insulin