Disease relevance of GPR83

• Transduction of naive CD4+CD25- T cells with GPR83-encoding retroviruses did not confer in vitro suppressive activity [1].
• Nevertheless, GPR83-transduced T cells were able to inhibit the effector phase of a severe contact hypersensitivity reaction of the skin, indicating that GPR83 itself or GPR83-mediated signals conferred suppressive activity to conventional CD4+ T cells in vivo [1].
• The glucose infusion rate/body weight (GIR/BW), as measured using the hyperinsulinemic, euglycemic clamp technique, was unaltered during GH-replacement therapy [2].
• GIR was originally identified in murine thymoma cells, and shows a widespread, yet not completely complementary distribution in mouse and human brain [3].
• CONCLUSION:: In this small study, treatment with oral GSR (10 mg QD) was not significantly different from that of treatment with GIR (5 mg BID) with respect to short-term (12 weeks) FPG and HbA(1c) reductions in these ethnic Chinese adults with type 2 diabetes mellitus receiving treatment with a sulfonylurea [4].

High impact information on GPR83

• The circadian leptin cycles and the circadian cycles of total body insulin sensitivity (i.e., GIR, the glucose infusion rates needed to maintain euglycemia during hyperinsulinemic clamping) changed in a mirror image fashion [5].
• Our results suggest that GPR83 might be critically involved in the peripheral generation of Foxp3+ Treg cells in vivo [1].
• Expression of the mouse GIR gene is modulated by dexamethasone in the brain and periphery, suggesting that GIR function is directly responsive to glucocorticoid signals [3].
• Areas with moderate to high levels of GIR include olfactory regions such as the nucleus of olfactory tract, hippocampus, various thalamic nuclei, cortical layers, and some hypothalamic nuclei [3].
• GIR mRNA showed widespread distribution in forebrain limbic and thalamic structures, and a more restricted distribution in hindbrain areas such as the spinal trigeminal nucleus and the median raphe nucleus [3].

Chemical compound and disease context of GPR83

• Finally, PA-induced migration of MDA-MB-231 was markedly attenuated by pretreatment of cells with Clostridium difficile Toxin B, pertussis toxin and suramin, implying a role for a Gi receptor-dependent process involving activation of the small GTP-binding protein Rho [6].
• OBJECTIVE:: The aim of this study was to compare the efficacy and tolerability of a sustained-release glipizide (GSR) formulation with those of immediate-release glipizide (GIR) in Chinese patients with type 2 diabetes mellitus [4].

Biological context of GPR83

• Non-isotopic in situ hybridisation and radiation hybrid mapping have identified GPR72 to be localised on human chromosome 11q21.1, and GPR73 on human chromosome 2p14 [7].
• Y-receptor-like genes GPR72 and GPR73: molecular cloning, genomic organisation and assignment to human chromosome 11q21.1 and 2p14 and mouse chromosome 9 and 6 [7].
• Thirty-three normotensive IGT subjects were divided into three groups and twenty hypertensive IGT subjects were divided into two groups according to the degree of insulin resistance (GIR value) estimated by the euglycemic hyperinsulinemic clamp method [8].

Anatomical context of GPR83

• Furthermore, GPR83 was induced upon overexpression of Foxp3 in naive CD4+CD25- T cells [1].
• The mouse glucocorticoid-induced receptor (GIR) is an orphan G protein-coupled receptor highly expressed in brain and thymus (Harrigan et al., 1989; 1991) [9].
• In comparison with previous studies, significant regional differences exist in GIR distribution in mouse and rat brain, particularly in the thalamus, striatum and in hippocampus at a cellular level [3].
• The rat GIR was cloned from rat prefrontal cortex by our group and was shown to be up-regulated following chronic amphetamine [3].
• More specifically, high levels of GIR expression have been described in brain regions of mouse, rat and human including limbic forebrain and hypothalamic regions, suggesting a role for GIR in memory, cognition, stress, reward or the control of emotion [10].

Associations of GPR83 with chemical compounds

• Insulin activates guanosine 5'-[gamma-thio] triphosphate (GTP gamma S) binding to a novel GTP-binding protein, GIR, from human placenta [11].
• The lowest GIR was associated with higher fasting plasma insulin, increased insulin response to glucose, higher plasma triglyceride and uric acid, and lower high-density-lipoprotein cholesterol, but not with increased creatinine clearance rate in normotensive subjects [8].
• These experiments showed that even at low blood concentrations (<2 mM), ethanol caused a profound decrease in GIR, similar in magnitude to that observed at higher blood concentrations (approximately 40 mM)[12]
• Glucose infusion rates (GIR, mg.kg-1.min-1) were 17.0 +/- 0.9 in starch, 10.6 +/- 1.7 in sucrose, and 15.1 +/- 1.5 in sucrose with fish oil animals [13].
• A decrease in GIR was also observed in response to tert-butanol, an alcohol that is not a substrate for hepatic ADH [12].

Analytical, diagnostic and therapeutic context of GPR83

• Insulin sensitivity (glucose infusion rate, GIR) was measured by a euglycemic hyperinsulinemic clamp technique before and 2, 6 and 12 months after transplantation [14].
• The GIR values in the four recipients were normalized within 2 months and remained normal for 12 months after transplantation, despite long-term steroid therapy for immunosuppression [14].

References