GIP, along with
glucagon-like peptide-1 (GLP-1), belongs to a class of molecules referred to as
incretins,[7] which stimulate insulin release on oral food intake.
Synthesis and transport
GIP is derived from a 153-amino acid proprotein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. It is synthesized by K cells, which are found in the
mucosa of the
duodenum and the
jejunum of the
gastrointestinal tract.[8]
It has traditionally been named gastrointestinal inhibitory peptide or gastric inhibitory peptide and was found to decrease the secretion of
stomach acid[9] to protect the
small intestine from acid damage, reduce the rate at which
food is transferred through the
stomach, and inhibit the GI motility and secretion of acid. However, this is incorrect, as it was discovered that these effects are achieved only with higher-than-normal physiological level, and that these results naturally occur in the body through a similar
hormone,
secretin.[10]
It is now believed that the function of GIP is to induce
insulin secretion, which is stimulated primarily by
hyperosmolarity of
glucose in the duodenum.[11] After this discovery, some researchers prefer the new name of glucose-dependent insulinotropic peptide, while retaining the
acronym "GIP." The amount of insulin secreted is greater when glucose is administered orally than intravenously.[12]
In addition to its role as an incretin, GIP is known to inhibit
apoptosis of the pancreatic beta cells and to promote their proliferation. It also stimulates
glucagon secretion and fat accumulation. GIP receptors are expressed in many organs and tissues including the
central nervous system enabling GIP to influence
hippocampal memory formation and regulation of appetite and satiety.[13]
GIP recently appeared as a major player in
bone remodeling. Researchers at Universities of Angers and Ulster evidenced that genetic ablation of the GIP receptor in mice resulted in profound alterations of bone microarchitecture through modification of the adipokine network.[14] Furthermore, the deficiency in GIP receptors has also been associated in mice with a dramatic decrease in bone quality and a subsequent increase in fracture risk.[15] However, the results obtained by these groups are far from conclusive because their animal models give discordant answers and these works should be analysed very carefully.[citation needed]
Pathology
It has been found that
type 2 diabetics are not responsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics.[16] In research involving
knockout mice, it was found that absence of the GIP receptors correlates with resistance to
obesity.[17]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Meier JJ, Nauck MA (2005). "Glucagon-like peptide 1(GLP-1) in biology and pathology". Diabetes/Metabolism Research and Reviews. 21 (2): 91–117.
doi:
10.1002/dmrr.538.
PMID15759282.
S2CID39547553.
^Thorens B (Dec 1995). "Glucagon-like peptide-1 and control of insulin secretion". Diabète & Métabolisme. 21 (5): 311–8.
PMID8586147.
^Boron WF, Boulpaep EL (2009). Medical physiology: a cellular and molecular approach (2nd International ed.). Philadelphia, PA: Saunders/Elsevier.
ISBN9781416031154.
King MW (16 November 2006).
"Gastrointestinal Hormones and Peptides". Indiana University – Purdue University Indianapolis School of Medicine. Archived from
the original on 6 December 2007. Retrieved 1 October 2006.
Overview of all the structural information available in the
PDB for
UniProt: P09681 (Gastric inhibitory polypeptide) at the
PDBe-KB.