Store-operated calcium entry and diabetic complications

Abstract

Store-operated Ca 2þ entry (SOCE) is mediated by the store-operated Ca 2þ channel (SOC) that opens upon depletion of internal Ca 2þ stores following activation of G protein-coupled receptors or receptor tyrosine kinases. Over the past two decades, the physiological and pathological relevance of SOCE has been extensively studied. Recently, accumulating evidence suggests associations of altered SOCE with diabetic complications. This review focuses on the implication of SOCE as it pertains to various complications resulting from diabetes. We summarize recent findings by us and others on the involvement of abnormal SOCE in the development of diabetic complications, such as diabetic nephropathy and diabetic vasculopathy. The underlying mechanisms that mediate the diabetes-associated alterations of SOCE are also discussed. The SOCE pathway may be considered as a potential therapeutic target for diabetes-associated diseases.

Selective serotonin reuptake inhibitor, fluoxetine, impairs E-cadherin-mediated cell adhesion and alters calcium homeostasis in pancreatic beta cells

“…STIM1 protein functions as an ER Ca 2+ sensor, which clusters proximally to plasma membranes to activate Orai1 during ER Ca 2+ depletion 26 , 27 . Accumulating evidence indicates that altered SOCE is associated with diabetes complication 28 , 29 . Studies show that depletion of intracellular Ca 2+ stores in β cells activate SOCE 25 , 30 .…”

Reduced store‐operated Ca2+ entry impairs mesenteric artery function in response to high external glucose in type 2 diabetic ZDF rats

“…The relevance of SOCE for artery function in diabetes has been controversially discussed, 27 partly on account of inconsistent data obtained from different species, various models of diabetes, and diverse vascular beds. For example, a reduced SOCE‐dependent contraction has been measured in smooth muscle strips isolated from caudal arteries of type 2 diabetic Goto‐Kakizaki rats 28 .…”

Ca2+ entry via TRPC1 is essential for cellular differentiation and modulates secretion via the SNARE complex

“…SOCE was first identified as a major component of non-excitable cells, but further research has identified SOCE within a multitude of tissue types (Parekh and Putney, 2005). This knowledge has revealed it to be a ubiquitous Ca 2+ signaling pathway that regulates numerous cellular functions including those connected with diabetic complications (Chaudhari and Ma, 2016). Identification of SOCE mechanisms within adipocytes may lead to a better understanding of the onset of obesity and metabolic disorders and reveal therapeutic possibilities.…”