Measurements of Cytoplasmic Ca2+ in Islet Cell Clusters Show That Glucose Rapidly Recruits β-Cells and Gradually Increases the Individual Cell Response

• Published in: Diabetes (New York, N.Y.) Vol. 50; no. 3; pp. 540 - 550
• Main Authors: JONKERS, Francoise C, HENQUIN, Jean-Claude
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.03.2001
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cytoplasm - metabolism; Endocrine pancreas; Female; Fundamental and applied biological sciences. Psychology; Glucose - pharmacology; Hormones. Régulation; In Vitro Techniques; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - cytology; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Mice; Mice, Inbred Strains; Osmolar Concentration; Vertebrates: endocrinology; Human; Pancreatic hormone; Calcium; Langerhans islet; Glucose; Inorganic element; Insulin; Endocrine pancreas; Endocrine secretion
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.50.3.540

Measurements of Cytoplasmic Ca 2+ in Islet Cell Clusters Show That Glucose Rapidly Recruits β-Cells and Gradually Increases the Individual Cell Response Françoise C. Jonkers and Jean-Claude Henquin Unité d’Endocrinologie et Métabolisme, University of Louvain Faculty of Medicine, Brussels, Belgium Abstract The proportion of isolated single β-cells developing a metabolic, biosynthetic, or secretory response increases with glucose concentration (recruitment). It is unclear whether recruitment persists in situ when β-cells are coupled. We therefore measured the cytoplasmic free Ca 2+ correction ([Ca 2+ ] i ) (the triggering signal of glucose-induced insulin secretion) in mouse islet single cells or clusters cultured for 1–2 days. In single cells, the threshold glucose concentration ranged between 6 and 10 mmol/l, at which concentration a maximum of ∼65% responsive cells was reached. Only 13% of the cells did not respond to glucose plus tolbutamide. The proportion of clusters showing a [Ca 2+ ] i rise increased from ∼20 to 95% between 6 and 10 mmol/l glucose, indicating that the threshold sensitivity to glucose differs between clusters. Within responsive clusters, 75% of the cells were active at 6 mmol/l glucose and 95–100% at 8–10 mmol/l glucose, indicating that individual cell recruitment is not prominent within clusters; in clusters responding to glucose, all or almost all cells participated in the response. Independently of cell recruitment, glucose gradually augmented the magnitude of the average [Ca 2+ ] i rise in individual cells, whether isolated or associated in clusters. When insulin secretion was measured simultaneously with [Ca 2+ ] i , a good temporal and quantitative correlation was found between both events. However, β-cell recruitment was maximal at 10 mmol/l glucose, whereas insulin secretion increased up to 15–20 mmol/l glucose. In conclusion, β-cell recruitment by glucose can occur at the stage of the [Ca 2+ ] i response. However, this type of recruitment is restricted to a narrow range of glucose concentrations, particularly when β-cell association decreases the heterogeneity of the responses. Glucose-induced insulin secretion by islets, therefore, cannot entirely be ascribed to recruitment of β-cells to generate a [Ca 2+ ] i response. Modulation of the amplitude of the [Ca 2+ ] i response and of the action of Ca 2+ on exocytosis (amplifying actions of glucose) may be more important. [Ca2+]i, cytoplasmic free Ca2+ concentration Footnotes Address correspondence and reprint requests to Dr. J.-C. Henquin, Unité d’Endocrinologie et Metabolisme, UCL 55.30, avenue Hippocrate 55, B-1200 Brussels, Belgium. E-mail: henquin{at}endo.ucl.ac.be . Received for publication 14 April 2000 and accepted in revised form 1 December 2000.