The Anx7(+/-) Knockout Mutation Alters Electrical and Secretory Responses to Ca2+-Mobilizing Agents in Pancreatic β-cells

Cellular Physiology and Biochemistry

关键词: Islet of Langerhans;    Insulin secretion;    IP3 receptor;    Ryanodine receptor;    Stimulus-secretion coupling;    Endoplasmic reticulum;    Annexin 7;    Knockout mouse;   

DOI  :  10.1159/000186926

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Insulin secretion from the pancreatic β-cell is controlled by changes in membrane potential and intracellular Ca²⁺. The contribution of intracellular Ca²⁺ stores to this process is poorly understood. We have previously shown that β-cells of mice lacking one copy of the Annexin 7 gene (Anx7(+/-)) express reduced levels of IP₃ receptors and defects in IP₃-dependent Ca²⁺ signaling. To further elucidate the effect of the Anx7(+/-) mutation on signaling related to intracellular Ca²⁺ stores in the β-cell, we measured the effects of Ca²⁺ mobilizing agents on electrical activity, intracellular Ca²⁺ and insulin secretion in control and mutant β-cells. We found that the muscarinic agonist carbachol and the ryanodine receptor agonists caffeine and 4-chloro-m-cresol had more potent depolarizing effects on Anx7(+/-) β-cells compared to controls. Accordingly, glucose-induced insulin secretion was augmented to a greater extent by caffeine in mutant islets. Surprisingly, ryanodine receptor-mediated Ca²⁺ mobilization was not affected by the Anx7(+/-) mutation, suggesting that the mechanism underlying the observed differences in electrical and secretory responsiveness does not involve intracellular Ca²⁺ stores. Our results provide evidence that both IP3 receptors and ryanodine receptors play important roles in regulating β-cell membrane potential and insulin secretion, and that the Anx7(+/-) mutation is associated with alterations in the signaling pathways related to these receptors.

【 授权许可】

CC BY-NC-ND