The extracellular calcium-sensing receptor on human β-cells negatively modulates insulin secretion

Squires, Paul E. and Harris, T. E. and Persaud, S. J. and Curtis, S. B. and Buchan, A. M. J. and Jones, P. M. (2000) The extracellular calcium-sensing receptor on human β-cells negatively modulates insulin secretion. Diabetes, 49 (3). pp. 409-417. ISSN 0012-1797

Full content URL: http://diabetes.diabetesjournals.org/content/49/3/...

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Item Type:Article
Item Status:Live Archive

Abstract

The presence and functional significance of the extracellular calcium- sensing receptor (CAR) on human pancreatic β-cells were investigated. Reverse transcriptase-polymerase chain reaction with primers for the extracellular domain of the CaR expressed in human parathyroid-secreting cells identified a product of the expected size in human pancreatic mRNA. Immunocytochemistry using an antibody against the extracellular region of CaR showed extensive immunoreactivity in insulin- and glucagon-containing cells but not in somatostatin-containing cells. In perifusion experiments, elevations in extracellular Ca2+ produced initial transient increases in insulin secretion, followed by a concentration-dependent and prolonged, but reversible, inhibition of secretion. Microfluorometric measurements of intracellular Ca2+ (Ca2+(i) in isolated human β-cells demonstrated that elevations in extracellular Ca2+ (0.5-10 mmol/l) caused rapid elevations in Ca2+(i). Increases in extracellular Ca2+ caused small increases in the cyclic AMP content of whole human islets. These studies demonstrated that human β-cells express an extracellular CaR and that activation of the receptor inhibits basal and nutrient-stimulated insulin secretion. The transduction mechanism that mediates this inhibitory effect is unknown, but our results suggest that it is unlikely to be through the adenylate cyclase-cyclic AMP pathway or through the phopholipase C-IP3 pathway. This CaR-mediated inhibitory mechanism may be an important autoregulatory mechanism in the control of insulin secretion.

Keywords:adenylate cyclase, calcium, calcium sensing receptor, cyclic AMP, glucagon, insulin, phospholipase C, article, calcium cell level, human, human cell, immunoreactivity, insulin release, pancreas islet beta cell, parathyroid cell, priority journal, protein domain, signal transduction, Calcium, Extracellular Space, Humans, Islets of Langerhans, Pancreas, Receptors, Calcium-Sensing, Receptors, Cell Surface, RNA, Messenger
Subjects:C Biological Sciences > C990 Biological Sciences not elsewhere classified
Divisions:College of Science > School of Life Sciences
ID Code:14351
Deposited On:18 Jun 2014 15:06

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