Oscillations of sub-membrane ATP in glucose-stimulated beta cells depend on negative feedback from Ca2+

• DOI: 10.1007/s00125-013-2894-0
• Publication Date: 2013-03-27T15:49:28Z
• Authors: J. Li; H. Y. Shuai; E. Gylfe; A. Tengholm
• Keywords: Medicin och hälsovetenskap; Oscillations; Endocrinology, Diabetes and Metabolism; Medical and Health Sciences; Article; Mice; 03 medical and health sciences; Adenosine Triphosphate; Cell Line, Tumor; Insulin-Secreting Cells; Internal Medicine; Animals; Pancreatic beta cell; Human islets; 0303 health sciences; Perceval; Hydrogen-Ion Concentration; Mouse islets; ATP; Mice, Inbred C57BL; Ca2+; Glucose; Calcium; Female; Plasma membrane

ATP links changes in glucose metabolism to electrical activity, Ca(2+) signalling and insulin secretion pancreatic beta cells. There is evidence that cell oscillates, but little known about dynamics at the plasma membrane, where regulation of ion channels exocytosis occur.The sub-plasma-membrane concentration ([ATP]pm) was recorded cells intact mouse human islets using total internal reflection microscopy fluorescent reporter Perceval.Glucose dose-dependently increased [ATP]pm with half-maximal maximal effects 5.2 9 mmol/l, respectively. Additional elevations 11 20 mmol/l promoted pronounced oscillations were synchronised between neighbouring further disappeared when voltage-dependent influx prevented. In contrast, K(+)-depolarisation induced prompt lowering [ATP]pm. Simultaneous recordings ([Ca(2+)]pm) during early glucose-induced response revealed initial elevation preceded, temporarily interrupted by rise [Ca(2+)]pm. During subsequent oscillations, increases [Ca(2+)]pm correlated [ATP]pm.In cells, promotes [ATP]pm, which depend on negative feedback from . The bidirectional interplay these messengers sub-membrane space generates metabolic ionic underlie pulsatile secretion.