Human GAD2 (Glutamate decarboxylase 2) ELISA Kit

Aims The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing the production of the gamma-aminobutyric acid (GABA) which interacts with neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic islets, GABA serves as a functional regulator of pancreatic hormone release. Conflicting results have been reported concerning the potential impact of GAD2 variation on estimates of energy metabolism. The aim of this study was to elucidate potential associations between the GAD2-243A -> G polymorphism and levels of body mass index (BMI) and estimates of glycaemia. Methods Using high-throughput chip-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, the GAD2-243A -> G (rs2236418) polymorphism was genotyped in a population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White subjects. Results The G-allele was associated with modestly lower BMI (P = 0.01). In a case-control study of obesity, the G-allele frequency in 2582 participants with BMI < 25 kg/m(2) was 19.5% (18.4-20.6) compared with 17.1% (15.5-18.8) in 968 participants having BMI >= 30 kg/m(2) (P = 0.03), odds ratio 0.9 (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n = 206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)-related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383) 5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). Conclusion The present study suggests that the GAD2-243A -> G polymorphism in a population of middle-aged White people associates with a modest reduction in BMI and fasting and OGTT-related plasma glucose levels.

High levels of circulating prolactin are known to cause infertility, but the precise mechanisms by which prolactin influences the neuroendocrine axis are yet to be determined. We used dual-label in situ hybridization to investigate whether prolactin-receptor (PRLR) mRNA is expressed in GnRH neurons. In addition, because gamma-aminobutyric acidergic and kisspeptin neurons in the rostral hypothalamus are known to regulate GnRH neurons and, hence, might mediate the actions of prolactin, we investigated whether these neurons coexpress PRLR mRNA. (35)S-labeled RNA probes to detect PRLR mRNA were hybridized together with digoxigenin-labeled probes to detect either GnRH, Gad1/Gad2, or Kiss1 mRNA in the rostral hypothalamus of ovariectomized (OVX), estradiol-treated rats. Additional sets of serial sections were cut through the arcuate nucleus of OVX rats, without estradiol replacement, to examine coexpression of PRLR mRNA in the arcuate population of kisspeptin neurons. PRLR mRNA was highly expressed throughout the rostral preoptic area, particularly in periventricular regions surrounding the third ventricle, and there was a high degree of colocalization of PRLR mRNA in both Gad1/Gad2 and Kiss1 mRNA-containing cells (86 and 85.5%, respectively). In contrast, only a small number of GnRH neurons (<5%) was found to coexpress PRLR mRNA. In the arcuate nucleus of OVX rats, the majority of Kiss1 mRNA-containing cells also coexpressed PRLR mRNA. These data are consistent with the hypothesis that, in addition to a direct action on a small subpopulation of GnRH neurons, prolactin actions on GnRH neurons are predominantly mediated indirectly, through known afferent pathways. (Endocrinology 152: 526-535, 2011)