GABA is known as a major inhibitory transmitter in the central nervous system, but has also been shown to be present with high concentrations in the pancreas [44,45,46]. interactions among islet cells under hypoglycemic conditions. Therefore, the mechanism by which glucagon secretion is reduced in hypoglycemia is still controversial, although it may be partially explained by insulin resistance in pancreatic cells. 3. Other Islet Cell Factors Regulating Glucagon Secretion Paracrine signaling indicates that secretion from cells does not act on distant cells through the general circulation but acts on adjacent cells via direct diffusion and other similar mechanisms. In rodent islets, cells are found in the center of the islet and cells around the islets. Anatomically, paracrine factors from cells may affect Tolterodine tartrate (Detrol LA) cells, considering that blood flows from the central to the peripheral part in the islet [42]. By contrast, in human islets, islet cells are organized in a disorderly manner. However, human cells also have cells surrounding the blood vessels [43]. Therefore, it is possible to consider the influence of paracrine on Tolterodine tartrate (Detrol LA) pancreatic cells from pancreatic cells also in human. Just as insulin from cells suppresses glucagon secretion from cells, glucagon secretion from pancreatic cells is autocrinally and paracrinally regulated by various factors secreted by the pancreatic islet , , and cells. GABA, Zn2+, and insulin secreted by pancreatic cells suppress glucagon secretion from cells. GABA is known as a major inhibitory transmitter in the central nervous system, but has also been shown to be present with high concentrations in the pancreas [44,45,46]. In Tolterodine tartrate (Detrol LA) cells, GABA is synthesized from glutamine via the action of glutamic acid decarboxylase (GAD) and is released when the decellularization of cells occurs and the intracellular free Ca2+ concentration is increased. In mouse islets and cell lines (-TC1-9), GABA released from cells binds to the GABA-A receptors of cells and suppresses glucagon secretion [47,48,49]. Additionally, Zn2+ is contained in the insulin granules of pancreatic cells. In the perfused pancreas of rats, glucose-induced Zn2+ secretion from cells suppressed glucagon secretion [50]. However, in some reports that used mouse pancreatic islets, Zn2+ did not suppress glucagon secretion [51]. Furthermore, no changes were observed in glucose-induced glucagon secretion in Zn2+ granule transporter knockout mice [52]. Therefore, the contribution of Zn2+ in regulating glucagon secretion remains controversial. In addition, glucagon exocytosis in cells is inhibited by juxtacrine via the Ephin subtype A (EphA) of cells and EphA 4/7 Rabbit polyclonal to GNRH receptor of cells [53]. That is, glucagon secretion from pancreatic cells is suppressed by paracrine and juxtacrine from pancreatic cells. Somatostatin secreted by cells also suppresses glucagon secretion from cells similar to that from cells [54,55]. Somatostatin receptor (SSTR) subtype 2 is present in cells which suppresses glucose-induced glucagon secretion by reducing intracellular cAMP levels [32,56,57]. Moreover, glucagon secretion increased in isolated islets of SSTR2 knockout mice [58]. Somatostatin inhibits glucagon secretion in the pancreatic cell line InR1G9 cells [59]. Moreover, these reports have supported the notion that somatostatin suppresses glucagon secretion from cells. The suppression of arginine-induced glucagon secretion was observed in systemic somatostatin knockout mice. However, it did not affect basal glucagon secretion [60]. In addition, in rats, the administration of SSTR2-specific antagonists that inhibited insulin secretion with STZ treated mice did not alter blood glucagon levels [61]. That is, somatostatin suppresses glucagon secretion. However, somatostatin alone cannot completely suppress glucagon secretion. In addition, GRs are present in pancreatic cells [62,63,64]. Western blot and immunohistological staining confirmed the presence of GRs in human, mouse Tolterodine tartrate (Detrol LA) pancreatic islets and cell lines (-TC1-9) [65]. Glucagon secreted from cells binds to its own GR, promotes its own glucagon secretion via the cAMP-PKA pathways, and up-regulates its own gene expression in human and mouse islets and cell line (-TC1-9). In addition, the expression of Gcg mRNA decreased when glucagon receptor antagonists were added to mouse islets and -TC1-9 cells [65]. Therefore, glucagon secretion in pancreatic cells is controlled by other islet cells or themselves, and such.