Gastric inhibitory polypeptide

Gastric inhibitory polypeptide
Identifiers
Symbol GIP
Entrez 2695
HUGO 4270
OMIM 137240
RefSeq NM_004123
UniProt P09681
Other data
Locus Chr. 17 q21.3-q22

Gastric inhibitory polypeptide (GIP), also known as the glucose-dependent insulinotropic peptide, is an inhibiting hormone of the secretin family of hormones.[1]

GIP, along with glucagon-like peptide-1 (GLP-1), belongs to a class of molecules referred to as incretins.[2]

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.[3]

Like all endocrine hormones, it is transported by blood.

Gastric inhibitory polypeptide receptors are seven-transmembrane proteins found on beta-cells in the pancreas.

Functions

It has traditionally been named gastrointestinal inhibitory peptide or gastric inhibitory peptide and was found to decrease the secretion of stomach acid[4] 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.

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.[5] 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.[6]

GIP is also thought to have significant effects on fatty acid metabolism through stimulation of lipoprotein lipase activity in adipocytes. GIP release has been demonstrated in the ruminant animal and may play a role in nutrient partitioning in milk production (lipid metabolism). GIP is secreted in response to the first maternal feed (colostrum) in goat kids—GIP being measured via umbilical vein before its closure. For ethical reasons, GIP secretion has been demonstrated in humans only at approx 10 days of age. With respect to the role of GIP in lipid metabolism, supraphysiological levels have shown a lipogenic action, however the action of collagenase in experimental protocols is known to degrade GIP/ GIP receptors. GIP is part of the diffuse endocrine system and, as a consequence, difficult to demonstrate physiological or clinical effects. In comparison to insulin its effects are very subtle.

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.[7] 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.[8]

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.[9] In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.[10]

References

  1. ↑ Meier JJ, Nauck MA (2005). "Glucagon-like peptide 1(GLP-1) in biology and pathology". Diabetes/Metabolism Research and Reviews. 21 (2): 91–117. PMID 15759282. doi:10.1002/dmrr.538.
  2. ↑ Efendic S, Portwood N (2004). "Overview of incretin hormones". Hormone and Metabolic Research. 36 (11-12): 742–6. PMID 15655702. doi:10.1055/s-2004-826157.
  3. ↑ Costanzo, Linda (2014). Physiology. Philadelphia, PA: Saunders/Elsevier. p. 337. ISBN 9781455708475.
  4. ↑ Kim W, Egan JM (Dec 2008). "The role of incretins in glucose homeostasis and diabetes treatment". Pharmacological Reviews. 60 (4): 470–512. PMC 2696340 Freely accessible. PMID 19074620. doi:10.1124/pr.108.000604.
  5. ↑ Thorens B (Dec 1995). "Glucagon-like peptide-1 and control of insulin secretion". Diabète & Métabolisme. 21 (5): 311–8. PMID 8586147.
  6. ↑ Boron WF, Boulpaep EL (2009). Medical physiology: a cellular and molecular approach (2nd International ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 9781416031154.
  7. ↑ Gaudin-Audrain C, Irwin N, Mansur S, Flatt PR, Thorens B, Baslé M, Chappard D, Mabilleau G (Mar 2013). "Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice". Bone. 53 (1): 221–30. PMID 23220186. doi:10.1016/j.bone.2012.11.039.
  8. ↑ Mieczkowska A, Irwin N, Flatt PR, Chappard D, Mabilleau G (Oct 2013). "Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality". Bone. 56 (2): 337–42. PMID 23851294. doi:10.1016/j.bone.2013.07.003.
  9. ↑ Skrha J, Hilgertová J, Jarolímková M, Kunešová M, Hill M (2010). "Meal test for glucose-dependent insulinotropic peptide (GIP) in obese and type 2 diabetic patients". Physiological Research. 59 (5): 749–55. PMID 20406045.
  10. ↑ Yamada Y, Seino Y (2004). "Physiology of GIP--a lesson from GIP receptor knockout mice". Hormone and Metabolic Research. 36 (11-12): 771–4. PMID 15655707. doi:10.1055/s-2004-826162.
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