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glucagon like peptide 1 receptor OKDB#: 5194
 Symbols: GLP1R Species: human
 Synonyms: GLP-1, GLP-1R, GLP-1-R  Locus: 6p21.2 in Homo sapiens
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General Comment Glucagon-like peptide-1 (GLP1) is a hormone derived from the preproglucagon molecule (GCG; 138030) and is secreted by intestinal L cells. It is the most potent stimulator of glucose-induced insulin secretion and also suppresses in vivo acid secretion by gastric glands. By transient expression of a rat pancreatic islet cDNA library in COS cells, Thorens (1992) isolated a cDNA for the GLP1 receptor (GLP1R). Transfected into COS cells, the receptor bound GLP1 with high affinity and was coupled to activation of adenylate cyclase. It did not bind peptides of related structure and similar function, such as glucagon (GCG; 138030), gastric inhibitory polypeptide (GIP; 137240), vasoactive intestinal peptide (VIP; 192320), or secretin (SCT; 182099). The receptor is 463 amino acids long and contains 7 transmembrane domains. Sequence homology was found only with the receptors for secretin (SCTR; 182098), calcitonin (CALCR; 114131), and parathyroid hormone (PTHR; 168468), which together form a newly characterized family of G protein coupled receptors.

NCBI Summary: This gene encodes a 7-transmembrane protein that functions as a receptor for glucagon-like peptide 1 (GLP-1) hormone, which stimulates glucose-induced insulin secretion. This receptor, which functions at the cell surface, becomes internalized in response to GLP-1 and GLP-1 analogs, and it plays an important role in the signaling cascades leading to insulin secretion. It also displays neuroprotective effects in animal models. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type 2 diabetes and stroke. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]
General function Receptor
Comment GLP-1 receptor agonists versus metformin in PCOS: a systematic review and meta-analysis. Han Y et al. (2019) This meta-analysis aimed to evaluate the efficacy and safety of glucagon-like peptide 1 (GLP-1) receptor agonists for women with polycystic ovary syndrome (PCOS) by comparing their effect with that of metformin. Electronic databases (PubMed, EMBASE, Cochrane Library, WanFang Database, CNKI) dating from their establishment to June 2018 were searched to find all randomized controlled trials (RCTs) reporting the efficacy of GLP-1 receptor agonists versus metformin for patients with PCOS. Therapeutic variables included menstrual cycle, sex hormone and clinical manifestations, glucose metabolism and other metabolic indexes. Eight RCTs among 462 related articles were included in the meta-analysis. Compared with metformin, GLP-1 receptor agonists were more effective in improving insulin sensitivity (standard mean difference [SMD] -0.40, 95% confidence interval [CI] -0.74 to -0.06, P = 0.02) and reducing body mass index (SMD -1.02, 95% CI -1.85 to -0.19, P = 0.02) and abdominal girth (SMD -0.45, 95% CI -0.89 to -0.00, P = 0.05). GLP-1 receptor agonists were associated with a higher incidence of nausea and headache than metformin, but there were no significant differences in other data. Therefore, compared with metformin, GLP-1 receptor agonists might be a good choice for obese patients with PCOS, especially those with insulin resistance. The available evidence is, however, inconclusive given its moderate to low quality. More high-quality research is needed to assess the efficacy of a GLP-1 receptor agonist on women with PCOS.//////////////////
Cellular localization Plasma membrane
Comment candidate123
Ovarian function
Comment
Expression regulated by
Comment
Ovarian localization
Comment GLP-1 increases pre-ovulatory LH source and the number of mature follicles, as well as synchronizing the onset of puberty in female rats. Outeiriño-Iglesias V et al. (2015) Control of estrous cycle and reproductive capacity involves a large number of central and peripheral factors, integrating numerous nutritional and metabolic signals. Here we show that GLP-1, a peptide with anorexigenic and insulinotropic actions, and the GLP-1 receptor agonist Exendin-4 exert a regulatory influence on the gonadal axis, in both adult and prepubertal female rats. In adult rats, Glp-1 receptor expression varies during the estrous cycle at the hypothalamus, pituitary and ovary. Furthermore, acute treatment with GLP-1 in the morning proestrus doubled the amplitude of the preovulatory LH surge, as well as influencing estradiol and progesterone levels along the estrous cycle. These changes provoked an important increase in the number of Graafian follicles and corpora lutea, as well as in the litter size. Conversely, Exendin-4 diminished the levels of LH, later producing a partial blockade at the preovulatory surge, yet not affecting either the number of mature follicles or corpora lutea. Chronic administration of low doses of GLP-1 to prepubertal rats synchronized vaginal opening and increased LH levels on the 35th day of life, yet at these doses it did not modify their body weight, food intake, or ovarian and uterine weight. By contrast, chronic exposure to Exendin-4 produced a significant reduction in ovarian and uterine weight, and serum LH, and the animals treated chronically with Exendin-4 showed no vaginal opening in the period studied. Overall, our results demonstrate that GLP-1 and Exendin-4 act on the gonadal axis, involving the hypothalamic Kiss-1 system, to influence reproductive efficiency in female rats.//////////////////
Follicle stages
Comment
Phenotypes PCO (polycystic ovarian syndrome)
Mutations 1 mutations

Species: human
Mutation name:
type: naturally occurring
fertility: subfertile
Comment: Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study. Jensterle M et al. (2015) The weight lowering potential of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) is inter-individually different and clinically unpredictable. The potential role of genetic variability of GLP-1R on body weight response to GLP-1 RAs in obese women with polycystic ovary syndrome (PCOS) has not yet been evaluated. Fifty-seven obese women with PCOS (aged 30.7 ± 7.0, BMI 38.6 ± 5.3 kg/m(2)) were assigned to liraglutide 1.2 mg QD s.c. for 12 weeks and classified as strong responders regarding weight loss if they lost 5 % or more of their initial body weight. They were genotyped for common GLP-1R single nucleotide polymorphisms (SNPs) rs6923761 and rs10305420. Changes of measures of obesity were measured before and at the end of the treatment. Twenty out of 57 subjects were strong responders and lost 7.38 ± 1.74 compared to 2.11 ± 2.17 kg lost in poor responders. Carriers of at least one polymorphic rs10305420 allele had poor treatment response compared to carriers of two wild type alleles (OR = 0.27, 95 % CI = 0.09-0.85, P = 0.025). Carriers of at least one polymorphic rs6923761 allele tended to have stronger treatment response compared to carriers of two wild type alleles (OR = 3.06, 95 % CI = 0.96-9.74, P = 0.058). Fasting glucose and glucose after oral glucose tolerance test (OGTT) comparably decreased in both groups when compared to baseline, whereas no within treatment differences were found in androgen profile. Gastrointestinal adverse events were transit and balanced between strong and poor responders. GLP-1R rs10305420 polymorphism explained some of the inter-individual differences in response to liraglutide regarding weight loss in obese PCOS women.//////////////////

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last update: March 20, 2020, 10:56 p.m. by: hsueh    email:



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