Cyclic adenosine monophosphate is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway. It should not be confused with 5'-AMP-activated protein kinase.
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It works to raise the concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers extracellular glucose. It is produced from proglucagon, encoded by the GCG gene.
Neuropeptides are small proteins produced by neurons that act on G protein-coupled receptors and are responsible for slow-onset, long-lasting modulation of synaptic transmission. Neuropeptides often coexist with each other or with other neurotransmitters in a single neuron. According to their chemical nature, coexisting messengers are localized to different cell compartments: neuropeptides are packaged in large dense core vesicles, whereas low-molecular weight neurotransmitters are stored in small synaptic vesicles.
Incretins are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood glucose-dependent mechanism.
Gastric inhibitory polypeptide (GIP), or gastric inhibitory peptide, also known as glucose-dependent insulinotropic polypeptide, is an inhibiting hormone of the secretin family of hormones. While it is weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion.
Proglucagon is a protein that is cleaved from preproglucagon. Preproglucagon in humans is encoded by the GCG gene.
Glucagon-like peptide-1 (GLP-1) is a 30 or 31 amino acid long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certain neurons within the nucleus of the solitary tract in the brainstem upon food consumption. The initial product GLP-1 (1–37) is susceptible to amidation and proteolytic cleavage which gives rise to the two truncated and equipotent biologically active forms, GLP-1 (7–36) amide and GLP-1 (7–37). Active GLP-1 composes two α-helices from amino acid position 13–20 and 24–35 separated by a linker region.
Peptide YY (PYY) also known as peptide tyrosine tyrosine is a peptide that in humans is encoded by the PYY gene. Peptide YY is a short peptide released from cells in the ileum and colon in response to feeding. In the blood, gut, and other elements of periphery, PYY acts to reduce appetite; similarly, when injected directly into the central nervous system, PYY is also anorexigenic, i.e., it reduces appetite.
The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in the activation of adenylate cyclase and phospholipase C and in increased levels of the secondary messengers intracellular cAMP and calcium. In humans, the glucagon receptor is encoded by the GCGR gene.
The glucagon-like peptide-1 receptor (GLP1R) is a receptor protein found on beta cells of the pancreas and on neurons of the brain. It is involved in the control of blood sugar level by enhancing insulin secretion. In humans it is synthesised by the gene GLP1R, which is present on chromosome 6. It is a member of the glucagon receptor family of G protein-coupled receptors. GLP1R is composed of two domains, one extracellular (ECD) that binds the C-terminal helix of GLP-1, and one transmembrane (TMD) domain that binds the N-terminal region of GLP-1. In the TMD domain there is a fulcrum of polar residues that regulates the biased signaling of the receptor while the transmembrane helical boundaries and extracellular surface are a trigger for biased agonism.
The gastric inhibitory polypeptide receptor (GIP-R), also known as the glucose-dependent insulinotropic polypeptide receptor, is a protein that in humans is encoded by the GIPR gene. GIP-R is a member of the 7-transmembrane protein family, a class of G protein
The Gs alpha subunit is a subunit of the heterotrimeric G protein Gs that stimulates the cAMP-dependent pathway by activating adenylyl cyclase. Gsα is a GTPase that functions as a cellular signaling protein. Gsα is the founding member of one of the four families of heterotrimeric G proteins, defined by the alpha subunits they contain: the Gαs family, Gαi/Gαo family, Gαq family, and Gα12/Gα13 family. The Gs-family has only two members: the other member is Golf, named for its predominant expression in the olfactory system. In humans, Gsα is encoded by the GNAS complex locus, while Golfα is encoded by the GNAL gene.
Glucagon-like peptide-2 receptor (GLP-2R) is a protein that in human is encoded by the GLP2R gene located on chromosome 17.
Pituitary adenylate cyclase-activating polypeptide type I receptor also known as PAC1, is a protein that in humans is encoded by the ADCYAP1R1 gene. This receptor binds pituitary adenylate cyclase activating peptide.
Secretin family receptor proteins, also known as Family B or family 2 of G-protein coupled receptors are regulated by peptide hormones from the glucagon hormone family. The family is different from adhesion G protein-coupled receptors.
Glucagon/GIP/secretin/VIP hormones are a family of evolutionarily related peptide hormones that regulate activity of G-protein coupled receptors from secretin receptor family.
Local hormones are a large group of signaling molecules that do not circulate within the blood. Local hormones are produced by nerve and gland cells and bind to either neighboring cells or the same type of cell that produced them. Local hormones are activated and inactivated quickly. They are released during physical work and exercise. They mainly control smooth and vascular muscle dilation. Strength of response is dependent upon the concentration of receptors of target cell and the amount of ligand.
2-Oleoylglycerol (2OG) is a monoacylglycerol that is found in biologic tissues. Its synthesis is derived from diacylglycerol precursors. It is metabolized to oleic acid and glycerol primarily by the enzyme monoacylglycerol lipase (MAGL). In 2011, 2OG was found to be an endogenous ligand to GPR119. 2OG has been shown to increase glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels following administration to the small intestine.
Teduglutide is a 33-membered polypeptide and glucagon-like peptide-2 (GLP-2) analog that is used for the treatment of short bowel syndrome. It works by promoting mucosal growth and possibly restoring gastric emptying and secretion. In Europe it has been granted orphan drug status and is marketed under the brand Revestive by Nycomed. It was approved by the United States under the name Gattex on 21 December 2012 and also is an orphan drug there.
The glucagon-like peptide receptors (GLPRs) include the following two receptors:
