SERCA3 ablation does not impair insulin secretion but suggests distinct roles of different sarcoendoplasmic reticulum Ca(2+) pumps for Ca(2+) homeostasis in pancreatic beta-cells

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 11; pp. 3245 - 3253
• Main Authors: Arredouani, Abdelilah, Guiot, Yves, Jonas, Jean-Christophe, Liu, Lynne H, Nenquin, Myriam, Pertusa, José A, Rahier, Jacques, Rolland, Jean-François, Shull, Gary E, Stevens, Martine, Wuytack, Frank, Henquin, Jean-Claude, Gilon, Patrick
• Format: Journal Article
• Language: English
• Published: United States 01.11.2002
• Subjects: Animals; Calcium - metabolism; Calcium Signaling - physiology; Calcium-Transporting ATPases - deficiency; Calcium-Transporting ATPases - genetics; Calcium-Transporting ATPases - metabolism; Exons; Glucose - physiology; Homeostasis; Immunohistochemistry; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - cytology; Islets of Langerhans - enzymology; Islets of Langerhans - physiology; Isoenzymes - genetics; Kinetics; Mice; Mice, Inbred Strains; Mice, Knockout; Reverse Transcriptase Polymerase Chain Reaction; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Time Factors
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.11.3245

Two sarcoendoplasmic reticulum Ca(2+)-ATPases, SERCA3 and SERCA2b, are expressed in pancreatic islets. Immunocytochemistry showed that SERCA3 is restricted to beta-cells in the mouse pancreas. Control and SERCA3-deficient mice were used to evaluate the role of SERCA3 in beta-cell cytosolic-free Ca(2+) concentration ([Ca(2+)](c)) regulation, insulin secretion, and glucose homeostasis. Basal [Ca(2+)](c) was not increased by SERCA3 ablation. Stimulation with glucose induced a transient drop in basal [Ca(2+)](c) that was suppressed by inhibition of all SERCAs with thapsigargin (TG) but unaffected by selective SERCA3 ablation. Ca(2+) mobilization by acetylcholine was normal in SERCA3-deficient beta-cells. In contrast, [Ca(2+)](c) oscillations resulting from intermittent glucose-stimulated Ca(2+) influx and [Ca(2+)](c) transients induced by pulses of high K(+) were similarly affected by SERCA3 ablation or TG pretreatment of control islets; their amplitude was increased and their slow descending phase suppressed. This suggests that, during the decay of each oscillation, the endoplasmic reticulum releases Ca(2+) that was pumped by SERCA3 during the upstroke phase. SERCA3 ablation increased the insulin response of islets to 15 mmol/l glucose. However, basal and postprandial plasma glucose and insulin concentrations in SERCA3-deficient mice were normal. In conclusion, SERCA2b, but not SERCA3, is involved in basal [Ca(2+)](c) regulation in beta-cells. SERCA3 becomes operative when [Ca(2+)](c) rises and is required for normal [Ca(2+)](c) oscillations in response to glucose. However, a lack of SERCA3 is insufficient in itself to alter glucose homeostasis or impair insulin secretion in mice.