1.
Intracellular and extracellular adenosine triphosphate in regulation of insulin secretion from pancreatic β cells (β).
Wang, C, Geng, B, Cui, Q, Guan, Y, Yang, J
Journal of diabetes. 2014;(2):113-9
Abstract
Adenosine triphosphate (ATP) synthesis and release in mitochondria play critical roles in regulating insulin secretion in pancreatic β cells. Mitochondrial dysfunction is mainly characterized by a decrease in ATP production, which is a central event in the progression of pancreatic β cell dysfunction and diabetes. ATP has been demonstrated to regulate insulin secretion via several pathways: (i) Intracellular ATP directly closes ATP-sensitive potassium channel to open L-type calcium channel, leading to an increase in free cytosolic calcium levels and exocytosis of insulin granules; (ii) A decrease in ATP production is always associated with an increase in production of reactive oxygen species, which exerts deleterious effects on pancreatic β cell survival and insulin secretion; and (iii) ATP can be co-secreted with insulin from pancreatic β cells, and the released ATP functions as an autocrine signal to modulate insulin secretory process via P2 receptors on the cell membrane. In this review, the recent findings regarding the role and mechanism of ATP synthesis and release in regulation of insulin secretion from pancreatic β cells will be summarized and discussed.
2.
[Expression of iPLA2 in human pancreatic islets and its important role in glucose-stimulated insulin secretion].
Wang, RT, Song, KY, Shi, JY, Lu, LS, Yang, J, Wang, QP, Li, K
Zhonghua yi xue za zhi. 2009;(20):1426-9
Abstract
OBJECTIVE To assess the role of calcium-independent phospholipase A2 (iPLA2) in human pancreatic islets. METHODS The immunohistochemical analysis and Western blot were employed to examine iPLA2 expression in human pancreatic islets. Bromoenol lactone (BEL), a selective inhibitor of iPLA2, was used in a randomized controlled trial to compare its influence to glucose-stimulated insulin secretion. RESULTS iPLA2 was expressed predominantly in islet cells co-stained by insulin but was barely detected in the exocrine acinar cells. Western blot results indicated that islet cells expressed an iPLA2-immunoreactive band at the 80 kDa region. Glucose-stimulated insulin secretory response was dramatically reduced in islets pretreated with BEL (0.8285 +/- 0.0803 ng x islet(-1) x h(-1)) as compared with the control (1.2264 +/- 0.0568 ng x islet(-1) x h(-1)) (P < 0.01). BEL inhibited glucose stimulated insulin secretion from isolated human islets. CONCLUSION iPLA2 signaling plays an important role in glucose-stimulated insulin secretion under the physiological conditions.