Azacyclonol australia br Cholecystokinin CCK CCK is secreted

Cholecystokinin (CCK) CCK is secreted by enteroendocrine I-cells of the duodenum and jejunum in response to amino acids and lipids [14]. There are two forms of the CCK receptor, CCK1 which is expressed on pancreatic α- and β-cells while CCK2 is located on somatostatin-secreting δ-cells [8]. CCK receptor activation augments insulin and glucagon release via Gαq protein, stimulating intracellular Ca2+ and PLC [8]. Intriguingly, CCK augments β-cell area in aged mice and protects from streptozotocin-induced diabetes [14].
Peptide YY (PYY) PYY is a 36 amino Azacyclonol australia peptide that is co-secreted from gastrointestinal enteroendocrine L-cells with GLP-1 and oxyntomodulin (OXM) [15]. Two major forms of PYY exists, PYY(1-36) and the truncated PYY(3-36) and the former is cleaved to the biologically active form PYY(3-36) by DPP-4 [16]. PPY levels are augmented following bariatric surgery and knockout rodent models implicate PYY as an essential peptide in weight loss following bypass surgery [15]. PYY stimulates these neuropeptide receptors Y1, Y4, Y5 and GPR83 which couple to Gαi, inhibiting cAMP production [8].
Oxyntomodulin (OXM) OXM is a 37 amino acid peptide produced from proglucagon that is co-secreted with GLP-1 and PYY from the gastrointestinal enteroendocrine L-cells in response to nutrient ingestion [15]. Biological actions of OXM include reducing food intake and body weight plus enhancing energy expenditure [17, 18•]. OXM is inactivated by the enzyme DPP-4 which was first identified when a DPP-4 inhibitor augmented OXM-induced satiety [17]. Interestingly, OXM is an agonist at both the GLP-1R and glucagon receptor, stimulating the adenylyl cyclase pathway with lower affinity compared to GLP-1 and glucagon [17].
Ghrelin Ghrelin is a 26 amino acid peptide which is secreted by enteroendocrine cells of the gastrointestinal tract and in pancreatic islets by α-cells and ɛ-cells [15]. Interestingly, ghrelin increases food intake and has a role in glucose homeostasis which may be due to enhanced insulin sensitivity [19]. The ghrelin receptor couples to the Gαi protein, decreasing membrane potential, intracellular Ca2+, cAMP production and insulin release from pancreatic β-cells [8].
Short chain fatty acid GPCRs GPR41 (FFAR3) is activated by short chain fatty acids (C3-C5) coupling to Gαi while GPR43 is activated by short chain fatty acids (C2-C3) coupling to Gαi and Gαq (Table 2) []. GPR41 is located on enteroendocrine L-cells which stimulates GLP-1 and PYY secretions and on pancreatic β-cells which may inhibit insulin release [20]. GPR43 (FFAR2) is expressed specifically on enteroendocrine L-cells affecting GLP-1 and PYY secretion and on pancreatic β-cells enhancing insulin release [20].
Medium chain fatty acid GPCRs GPR84 (previously known as EX33) is activated by medium chain fatty acids (C9-C14) and is expressed in immune cells, spleen, adipose tissue, pancreas, bone marrow and lung [21]. Activation of GPR84 results in coupling to Gαi inhibiting the adenylyl cyclase pathway, decreasing cAMP and PKA production [22].
Long chain fatty acid GPCRs GPR40 (free fatty acid receptor 1 (FFAR1)) is activated by long chain saturated and unsaturated fatty acids (C12-C16) that enhance glucose-stimulated insulin release from pancreatic β-cells []. Expression of GPR40 was identified on enteroendocrine cells including L-, K- and I-cells and upon activation releases GLP-1, GIP and CCK, respectively, a process which was blunted in GPR40 deficient mice [23]. GPR40 activation results in the coupling to Gαq subunit, enhancing PLC, IP3 and DAG which stimulates intracellular Ca2+ [24]. Synthetic agonists of GPR40 assessed in preclinical trials include GW-9508, TUG-424, AMG-837, AM-1638 and AS-2575959 improve glucose tolerance whereas GW-1100 has been identified as a specific antagonist [25]. GPR120 exhibits high affinity for saturated long chain fatty acids (C14-C18) and unsaturated fatty acids (C16-C22) [26]. Expression of GPR120 is predominantly found in the gastrointestinal tract, adipose tissue, lungs, spleen, pancreatic islets and immune cells [3•, 26]. In addition, GPR120 has a role in the secretion of GLP-1, GIP and CCK. GPR120 couples to Gαq, utilising the PKC pathway enhancing intracellular Ca2+ [3•, 26]. Recently, a dietary fatty acid pinolenic acid acted as a dual agonist at GPR40 and GPR120 and displayed potent antihyperglycaemic effects following oral glucose tolerance in C57BL/6 mice [27].