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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 a member 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]
Contents
- 1 Synthesis and transport
- 2 Function
- 3 Pathology
- 4 References
- 5 External links
Synthesis and transport[edit]
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.
Like all endocrine hormones, it is transported by blood.
Gastric inhibitory polypeptide receptors are seven-transmembrane proteins found on beta-cells in the pancreas.
Function[edit]
It has traditionally been called gastrointestinal inhibitory peptide or gastric inhibitory peptide and was believed to neutralize stomach acid[citation needed] 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.[3] 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.[4]
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 remodelling. 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.[5] Furthermore, deficiency in GIP receptors has also been associated in mice with a dramatic decrease in bone quality and a subsequent increase in fracture risk.[6]
Pathology[edit]
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.[7] In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.[8]
References[edit]
- ^ Meier JJ, Nauck MA (2005). "Glucagon-like peptide 1(GLP-1) in biology and pathology". Diabetes Metab. Res. Rev. 21 (2): 91–117. doi:10.1002/dmrr.538. PMID 15759282.
- ^ Efendic S, Portwood N (2004). "Overview of incretin hormones". Horm. Metab. Res. 36 (11–12): 742–6. doi:10.1055/s-2004-826157. PMID 15655702.
- ^ Thorens B (1995). "Glucagon-like peptide-1 and control of insulin secretion". Diabète & métabolisme 21 (5): 311–8. PMID 8586147.
- ^ Boulpaep, [edited by] Walter F. Boron, Emile L. (2009). Medical physiology : a cellular and molecular approach (2nd ed., International ed. ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 9781416031154.
- ^ Gaudin-Audrain C, Irwin N, Mansur S, Flatt PR, Thorens B, Basle M, Chappard D, Mabilleau G (2013). "Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice". Bone 53 (1): 221–30. doi:10.1016/j.bone.2012.11.039. PMID 23220186.
- ^ Mieczkowska A, Irwin N, Flatt PR, Chappard D, Mabilleau G (2013). "Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality". Bone 56 (2): 337–42. doi:10.1016/j.bone.2013.07.003. PMID 23851294.
- ^ 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". Physiol Res 59 (5): 749–55. PMID 20406045.
- ^ Yamada Y, Seino Y (2004). "Physiology of GIP—a lesson from GIP receptor knockout mice". Horm. Metab. Res. 36 (11–12): 771–4. doi:10.1055/s-2004-826162. PMID 15655707.
External links[edit]
- Gastric inhibitory polypeptide at the US National Library of Medicine Medical Subject Headings (MeSH)
- Gastric+inhibitory+polypeptide at eMedicine Dictionary
- http://web.indstate.edu/thcme/mwking/peptide-hormones.html#gastrin
Endocrine system: hormones (Peptide hormones · Steroid hormones)
|
|
Endocrine
glands |
Hypothalamic-
pituitary
|
Hypothalamus
|
GnRH · TRH · Dopamine · CRH · GHRH/Somatostatin · Melanin concentrating hormone
|
|
Posterior pituitary
|
Vasopressin · Oxytocin
|
|
Anterior pituitary
|
α (FSH FSHB, LH LHB, TSH TSHB, CGA) · Prolactin · POMC (CLIP, ACTH, MSH, Endorphins, Lipotropin) · GH
|
|
|
Adrenal axis
|
Adrenal cortex: aldosterone · cortisol · DHEA
Adrenal medulla: epinephrine · norepinephrine
|
|
Thyroid axis
|
Thyroid: thyroid hormone (T3 and T4) · calcitonin
Parathyroid: PTH
|
|
Gonadal axis
|
Testis: testosterone · AMH · inhibin
Ovary: estradiol · progesterone · activin and inhibin · relaxin (pregnancy)
Placenta: hCG · HPL · estrogen · progesterone
|
|
Islet-Acinar
Axis
|
Pancreas: glucagon · insulin · amylin · somatostatin · pancreatic polypeptide
|
|
Pineal gland
|
Pineal gland: melatonin
|
|
|
Non-end.
glands |
Thymus: Thymosin (Thymosin α1, Thymosin beta) · Thymopoietin · Thymulin
Digestive system: Stomach: gastrin · ghrelin · Duodenum: CCK · Incretins (GIP, GLP-1) · secretin · motilin · VIP · Ileum: enteroglucagon · peptide YY · Liver/other: Insulin-like growth factor (IGF-1, IGF-2)
Adipose tissue: leptin · adiponectin · resistin
Skeleton: Osteocalcin
Kidney: JGA (renin) · peritubular cells (EPO) · calcitriol · prostaglandin
Heart: Natriuretic peptide (ANP, BNP)
|
|
|
|
noco (d)/cong/tumr, sysi/epon
|
proc, drug (A10/H1/H2/H3/H5)
|
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|
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Digestive system, physiology: gastrointestinal physiology
|
|
GI tract |
Upper GI
|
Exocrine
|
Chief cells (Pepsinogen) · Parietal cells (Gastric acid, Intrinsic factor) · Goblet cells (Mucus)
|
|
Processes
|
Swallowing · Vomiting
|
|
Fluids
|
Saliva · Gastric juice
|
|
|
Lower GI
|
Enteric nervous system
|
Meissner's plexus · Auerbach's plexus
|
|
Endocrine/paracrine
|
G cells (gastrin) · D cells (somatostatin) · ECL cells (Histamine)
enterogastrone: I cells (CCK) · K cells (GIP) · S cells (secretin)
Enteroendocrine cells · Enterochromaffin cell · APUD cell
|
|
Fluids
|
Intestinal juice
|
|
Processes
|
Segmentation contractions · Migrating motor complex · Borborygmus · Defecation
|
|
|
Either/both
|
Processes
|
Peristalsis (Interstitial cell of Cajal · Basal electrical rhythm) · Gastrocolic reflex · Digestion
|
|
|
|
Accessory |
Fluids
|
Bile · Pancreatic juice
|
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Processes
|
Enterohepatic circulation
|
|
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Abdominopelvic |
Peritoneal fluid
|
|
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anat (t, g, p)/phys/devp/enzy
|
noco/cong/tumr, sysi/epon
|
proc, drug (A2A/2B/3/4/5/6/7/14/16), blte
|
|
|
|
Endocrine system: hormones (Peptide hormones · Steroid hormones)
|
|
Endocrine
glands |
Hypothalamic-
pituitary
|
Hypothalamus
|
GnRH · TRH · Dopamine · CRH · GHRH/Somatostatin · Melanin concentrating hormone
|
|
Posterior pituitary
|
Vasopressin · Oxytocin
|
|
Anterior pituitary
|
α (FSH FSHB, LH LHB, TSH TSHB, CGA) · Prolactin · POMC (CLIP, ACTH, MSH, Endorphins, Lipotropin) · GH
|
|
|
Adrenal axis
|
Adrenal cortex: aldosterone · cortisol · DHEA
Adrenal medulla: epinephrine · norepinephrine
|
|
Thyroid axis
|
Thyroid: thyroid hormone (T3 and T4) · calcitonin
Parathyroid: PTH
|
|
Gonadal axis
|
Testis: testosterone · AMH · inhibin
Ovary: estradiol · progesterone · activin and inhibin · relaxin (pregnancy)
Placenta: hCG · HPL · estrogen · progesterone
|
|
Islet-Acinar
Axis
|
Pancreas: glucagon · insulin · amylin · somatostatin · pancreatic polypeptide
|
|
Pineal gland
|
Pineal gland: melatonin
|
|
|
Non-end.
glands |
Thymus: Thymosin (Thymosin α1, Thymosin beta) · Thymopoietin · Thymulin
Digestive system: Stomach: gastrin · ghrelin · Duodenum: CCK · Incretins (GIP, GLP-1) · secretin · motilin · VIP · Ileum: enteroglucagon · peptide YY · Liver/other: Insulin-like growth factor (IGF-1, IGF-2)
Adipose tissue: leptin · adiponectin · resistin
Skeleton: Osteocalcin
Kidney: JGA (renin) · peritubular cells (EPO) · calcitriol · prostaglandin
Heart: Natriuretic peptide (ANP, BNP)
|
|
|
|
noco (d)/cong/tumr, sysi/epon
|
proc, drug (A10/H1/H2/H3/H5)
|
|
|
|
Peptides: neuropeptides
|
|
Hormones |
see hormones
|
|
Opioid peptides |
Dynorphin
|
- Big dynorphin
- Dynorphin A
- Dynorphin B
|
|
Endorphins
|
- Beta-endorphin
- Alpha-endorphin
- Gamma-endorphin
- α-neo-endorphin
- β-neo-endorphin
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Enkephalin
|
- Met-enkephalin
- Leu-enkephalin
|
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Others
|
- Adrenorphin
- Amidorphin
- Leumorphin
- Nociceptin
- Opiorphin
- Spinorphin
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Other
neuropeptides |
Kinins
|
- Tachykinins: mammal
- Substance P
- Neurokinin A
- Neurokinin B
- amphibian
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Neuromedins
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Other
|
- Angiotensin
- Bombesin
- Calcitonin gene-related peptide
- Carnosine
- Cocaine and amphetamine regulated transcript
- Delta sleep-inducing peptide
- FMRFamide
- Galanin
- Galanin-like peptide
- Gastrin releasing peptide
- Neuropeptide S
- Neuropeptide Y
- Neurophysins
- Neurotensin
- Pancreatic polypeptide
- Pituitary adenylate cyclase activating peptide
- RVD-Hpα
- VGF
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B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
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