GCG
The protein encoded by this gene is actually a preproprotein that is cleaved into four distinct mature peptides. One of these, glucagon, is a pancreatic hormone that counteracts the glucose-lowering action of insulin by stimulating glycogenolysis and gluconeogenesis. Glucagon is a ligand for a specific G-protein linked receptor whose signalling pathway controls cell proliferation. Two of the other peptides are secreted from gut endocrine cells and promote nutrient absorption through distinct mechanisms. Finally, the fourth peptide is similar to glicentin, an active enteroglucagon. [provided by RefSeq, Jul 2008]
Function
Glucagon:
Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.
Glucagon-like peptide 1:
Potent stimulator of glucose-dependent insulin release. Also stimulates insulin release in response to IL6 (PubMed:22037645).
Plays important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Has growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis (Probable).
Glucagon-like peptide 2:
Stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.
Oxyntomodulin:
Significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.
Glicentin:
May modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.
Biological Process
Adenylate cyclase-activating G protein-coupled receptor signaling pathway Source: Ensembl
Adenylate cyclase-modulating G protein-coupled receptor signaling pathway Source: GO_Central
Feeding behavior Source: ProtInc
Glucose homeostasis Source: UniProtKB
G protein-coupled receptor signaling pathway Source: GO_Central
Negative regulation of apoptotic process Source: GO_Central
Negative regulation of execution phase of apoptosis Source: Ensembl
Positive regulation of calcium ion import Source: Ensembl
Positive regulation of ERK1 and ERK2 cascade Source: Ensembl
Positive regulation of gluconeogenesis Source: Ensembl
Positive regulation of histone H3-K4 methylation Source: Ensembl
Positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: GO_Central
Positive regulation of peptidyl-serine phosphorylation Source: Ensembl
Positive regulation of peptidyl-threonine phosphorylation Source: Ensembl
Positive regulation of protein binding Source: Ensembl
Positive regulation of protein kinase activity Source: Ensembl
Protein kinase A signaling Source: GO_Central
Regulation of insulin secretion Source: UniProtKB
Response to activity Source: UniProtKB
Cellular Location
Secreted
PTM
Proglucagon is post-translationally processed in a tissue-specific manner in pancreatic A cells and intestinal L cells. In pancreatic A cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In the intestinal L cells PCSK1/PC1 liberates GLP-1, GLP-2, glicentin and oxyntomodulin. GLP-1 is further N-terminally truncated by post-translational processing in the intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide. The C-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas.
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Datasheet