A Variant of GJD2, Encoding for Connexin 36, Alters the Function of Insulin Producing β-Cells.

Signalling through gap junctions contributes to control insulin secretion and, thus, blood glucose levels. Gap junctions of the insulin-producing β-cells are made of connexin 36 (Cx36), which is encoded by the GJD2 gene. Cx36-null mice feature alterations mimicking those observed in type 2 diabetes (T2D). GJD2 is also expressed in neurons, which share a number of common features with pancreatic β-cells. Given that a synonymous exonic single nucleotide polymorphism of human Cx36 (SNP rs3743123) associates with altered function of central neurons in a subset of epileptic patients, we investigated whether this SNP also caused alterations of β-cell function. Transfection of rs3743123 cDNA in connexin-lacking HeLa cells resulted in altered formation of gap junction plaques and cell coupling, as compared to those induced by wild type (WT) GJD2 cDNA. Transgenic mice expressing the very same cDNAs under an insulin promoter revealed that SNP rs3743123 expression consistently lead to a post-natal reduction of islet Cx36 levels and β-cell survival, resulting in hyperglycemia in selected lines. These changes were not observed in sex- and age-matched controls expressing WT hCx36. The variant GJD2 only marginally associated to heterogeneous populations of diabetic patients. The data document that a silent polymorphism of GJD2 is associated with altered β-cell function, presumably contributing to T2D pathogenesis

Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians

Copyright: Copyright 2008 Elsevier B.V., All rights reserved.The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.publishersversionPeer reviewe

Self-collisional broadening and shift coefficients of lines in the v₄+v₅ band of C₂¹²H₂ from 173.2 to 298.2K by diode-laser spectroscopy

International audienceThe pressure-induced self-shift and broadening coefficients for seven lines of 12C2H2 in the nu4+nu5 band located around 1330 cm−1 have been measured using a tunable diode-laser spectrometer coupled with a low temperature absorption cell. The measurement of these coefficients was realized at five temperatures ranging from 173.2 to 273.2 K (and also 298.2 K for shift) in order to determine their temperature dependence. The broadening coefficients were obtained by fitting to the experimental profile the Voigt lineshape and the Rautian and the Galatry models which take into account the collisional narrowing due to molecular confinement (Dicke effect). The shift coefficients were determined using a procedure, where calibration lines were simultaneously recorded with transitions from the gas sample under study. The results have been compared with previous experimental data. Our coefficients of collisional broadening, gamma0, as well as the temperature dependence parameters, n, are in satisfactory agreement with previous studies. The pressure broadening coefficients, gamma0, are in good agreement with those reported for various vibrational bands, indicating that they are insensitive to vibrational excitation. The pressure shift coefficients, delta0, by contrast, are found to differ substantially among vibrational bands

Collisional broadening and shift coefficients of lines in the band of C2H2 diluted in N2 from low to room temperatures

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