Abstract
Glucagon, secreted from islet alpha cells, plays an important role in regulating glucose homeostasis; however, the molecular mechanism underlying this process is not fully understood. Previous studies have demonstrated that miRNAs are involved in the function of alpha cells. Glutamate promotes glucagon secretion by mediating the opening of Ca2+ channels. In this present, iGluR2 and iGluR3 levels were significantly increased in fasting-treated mouse islets. Additional studies showed that miR-124-3p simultaneously regulates the expression of iGluR2 and iGluR3 through the direct targeting of mRNA 3’UTR of these two genes. The miR-124-iGluRs pathway also contributed to the high level of glucagon secretion through long-term high glucose levels. Thus, a novel pathway comprising miRNA, glutamate and iGluRs has been demonstrated to regulate the biological process of glucagon release.
Highlights
Human blood glucose plays an important role in the control of physiological functions and is regulated through the conversion of pancreatic hormones secretion from different cell types in islets
Studies have reported that iGluR2 and iGluR3 are expressed in pancreatic α cells but not in beta cells, and these receptors positively regulate glucagon release14
To evaluate the expression of iGluR2 and iGluR3 in alpha cells when blood glucose levels are reduced, the mice were fasted for 12 h, and the islets were isolated, followed
Summary
Human blood glucose plays an important role in the control of physiological functions and is regulated through the conversion of pancreatic hormones secretion from different cell types in islets. Insulin and glucagon, secreted from pancreatic beta and alpha cells, respectively, are two important hormones that regulate glucose homeostasis. Previous studies have been focused on the molecular mechanisms underlying insulin synthesis and release [6, 7]; the biological process of glucagon secretion is not fully understood. Recent studies have demonstrated that glutamate secreted from α cells is essential for glucagon release [8]. Studies have shown that pancreatic α cells express glutamate, and glutamate is secreted into the vesicles together with glucagon [10, 11]. Glutamate acts on AMPA/kainite type ionotropic glutamate receptors (iGluRs), followed by the opening of Ca2+ channels, the increase of the Ca2+ concentration in the cytoplasm, and the enhanced secretion of glucagon. The molecular mechanisms that regulate iGluRs expression in the process of glucagon release remain unknown
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