Disease relevance of Gipr

• We previously demonstrated that sequences between -1 and -100 of the GIPR gene were sufficient to direct transcription in a rat insulinoma cell line (RIN38) [1].
• And we also revealed some genetic events in the early stage of diabetic retinopathy including the de novo increment of GIP and GIPR expression in the retina [2].
• However, semi-quantitative RT-PCR revealed that the ratio of the gene expression level of the GIP receptor to that of the GLP-1 receptor was less than 1:250, indicating that receptor gene expression of GIP is practically negligible in the ganglion [3].

High impact information on Gipr

• Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat [4].
• Similar protective effects were found with dispersed islet cells from C57BL/6 mice, but not with those from GIP receptor knock-out (GIPR(-/-)) mice [5].
• GIP treatment reduced glucolipotoxicity-induced cell death in C57 BL/6 and Bax(-/-) islets, but not GIPR(-/-) mouse islets [5].
• A screening technique was used to determine the relative abundance of 75 protein kinases in CHO-K1 cells expressing the GIP receptor and in two pancreatic beta-cell lines (betaTC-3 and INS-1 (832/13) cells) [6].
• Fasting plasma glucose levels were not altered by GIPR Ab [7].

Biological context of Gipr

• Lastly, chromatin immunoprecipitation analyses revealed that both Sp1 and Sp3 bind to the GIPR promoter region in RIN38 cells [1].
• The cellular basis of down-regulation and chronic desensitization of GIP-R is unclear [8].
• We conclude that a saturable [125I]GIP binding site with the pharmacological properties of an authentic GIP receptor is expressed in certain regions of the rat brain [9].
• The results of these studies indicate that GIP gene expression is enhanced in diabetic animals and that elevated serum GIP level induces chronic desensitization of the GIP receptor in vivo and in a stably transfected cell line [10].
• Competitive-binding displacement studies indicated that these peptides were low-affinity ligands for the GIP receptor [11].

Anatomical context of Gipr

• The hypothesis of the present study is that one cause of decreased responsiveness to GIP in type 2 diabetes is an inappropriate expression of the GIP receptor in the pancreatic islet [12].
• Finally, in hyperglycemic clamped rats, there was a 70% reduction in GIPR expression in the islets and a 71% reduction in GIP-stimulated insulin secretion from the perfused pancreas [13].
• Antisera to an extracellular epitope of the GIP receptor (GIPR) detected immunoreactive GIPR on rat pancreatic beta-cells [7].
• RNAse protection analysis demonstrated the presence of GIP receptor transcripts in rat adipocytes [14].
• A polyclonal GIP receptor antiserum directed at the N-terminus of the receptor detected the presence of GIP receptors in both rat fat and differentiated 3T3-L1 cells by Western blot analysis [14].

Associations of Gipr with chemical compounds

• High (25 mM) glucose was able to significantly reduce GIPR mRNA levels in INS(832/13) cells after only 6 h [13].
• In contrast, palmitic acid (2 mM) and WY 14643 (100 microM) stimulated approximate doublings of GIPR expression in INS(832/13) cells under low (5.5 mM), but not high (25 mM), glucose conditions, suggesting that fat can regulate GIPR expression via PPARalpha in a glucose-dependent manner [13].
• The data suggest that chronic desensitization and down-regulation of the GIP-R may be mediated by similar mechanisms, and that the cysteine in the carboxyl terminus plays an essential role in regulating both processes [8].
• GIP-receptor mRNA has been detected in the rat adrenal cortex, but investigations on the effect of GIP on steroid-hormone secretion in this species are lacking [15].
• Peptides were screened for stimulation of cyclic AMP (cAMP) accumulation in Chinese hamster ovary cells transfected with the rat islet GIP receptor [11].

Regulatory relationships of Gipr

• Treatment with GIPR Ab (1 microg/g BW) blocked the potentiation of glucose-stimulated insulin secretion by GIP (60 pmol) but not glucagon-like peptide-1 (GLP-1, 60 pmol) in anesthetized rats [7].

Analytical, diagnostic and therapeutic context of Gipr

• As to the GIP receptor, RT-PCR amplified the gene transcript faintly though Northern blot analysis failed to detect any messages [3].

References