Gastric inhibitory polypeptide, also known as glucose-dependent insulinotropic polypeptide (GIP), is a 42-amino acid peptide that plays an important role in maintaining glucose and lipid homeostasis. Although originally discovered as an inhibitor of gastric acid secretion, its principal physiological property is its role as an incretin peptide, in which it mediates the enteroinsular axis. GIP is synthesized by enteroendocrine K-cells of the duodenum/proximal jejunum, and its secretion is stimulated postprandially. GIP signaling stimulates glucose absorption in enterocytes, potentiates endogenous glucose-dependent insulin release from islet beta-cells, increases glucose uptake while inhibiting lipolysis in adipocytes, increases nutrient uptake into bone, and inhibits bone resorption [1].
The competition binding experiments were carried out in transiently transfected COS-7 cells using 125I GIP as radioligand. For the homologous competition binding, an IC50 value of 5.2 nM was observed [2]. GIP receptor messenger RNA was detected by RT-PCR and RNase protection assay. Receptors were detected in binding studies (IC50 26.7 +/- 0.7 nM). GIP stimulated glycerol release with an EC50 of 3.28 +/- 0.63 nM [3].
Perfusion of the pancreas with 1 nM GIP increased insulin secretion significantly (P[2]. The effects of GIP on fat metabolism in vivo may depend upon the circulating insulin level, and that meal-released GIP may elevate circulating fatty acids, thus optimizing pancreatic β-cell responsiveness to stimulation by glucose and GIP [3].
References:
[1].Zhang CY, Boylan MO, Arakawa H, Wolfe MM. Effects of gastric inhibitory polypeptide (GIP) immunoneutralization on mouse motor coordination and memory. Peptides. 2020 Mar;125:170227.
[2].Deacon CF, Plamboeck A, Rosenkilde MM, de Heer J, Holst JJ. GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations. Am J Physiol Endocrinol Metab. 2006 Sep;291(3):E468-75.
[3].McIntosh CH, Bremsak I, Lynn FC, Gill R, Hinke SA, Gelling R, Nian C, McKnight G, Jaspers S, Pederson RA. Glucose-dependent insulinotropic polypeptide stimulation of lipolysis in differentiated 3T3-L1 cells: wortmannin-sensitive inhibition by insulin. Endocrinology. 1999 Jan;140(1):398-404.
胃抑制多肽,也称为葡萄糖依赖性促胰岛素多肽 (GIP),是一种由 42 个氨基酸组成的肽,在维持葡萄糖和脂质稳态方面发挥着重要作用。虽然最初被发现是胃酸分泌的抑制剂,但其主要生理特性是其作为肠促胰岛素肽的作用,在该肽中它介导肠岛叶轴。 GIP 由十二指肠/近端空肠的肠内分泌 K 细胞合成,其分泌在餐后受到刺激。 GIP 信号刺激肠细胞对葡萄糖的吸收,增强胰岛 β 细胞释放内源性葡萄糖依赖性胰岛素,增加葡萄糖摄取,同时抑制脂肪细胞的脂肪分解,增加骨骼对营养的摄取,并抑制骨吸收[1] .
竞争结合实验是在瞬时转染的 COS-7 细胞中进行的,使用 125I GIP 作为放射配体。对于同源竞争结合,观察到 IC50 值为 5.2 nM [2]。通过RT-PCR和RNase保护试验检测GIP受体信使RNA。在结合研究中检测到受体 (IC50 26.7 +/- 0.7 nM)。 GIP 刺激甘油释放,EC50 为 3.28 +/- 0.63 nM [3]。
用 1 nM GIP 灌注胰腺可显着增加胰岛素分泌（P[2]。GIP 对体内脂肪代谢的影响可能取决于循环中的胰岛素水平,而膳食释放的GIP 可能会增加循环脂肪酸,从而优化胰腺 β 细胞对葡萄糖和 GIP 刺激的反应性[3]。