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941.
O Burnicka-Turek BA Mohamed K Shirneshan T Thanasupawat S Hombach-Klonisch T Klonisch IM Adham 《Endocrinology》2012,153(10):4655-4665
Insulin-like factor 5 (INSL5), a member of the insulin superfamily, is expressed in the colorectum and hypothalamus. To facilitate studies into the role of INSL5, we generated Insl5(-/-) mice by gene targeting. Insl5(-/-) mice were born in the expected Mendelian ratio, reached normal body weight, but displayed impaired male and female fertility that are due to marked reduction in sperm motility and irregular length of the estrous cycle. Furthermore, Insl5(-/-) mice showed impairment in glucose homeostasis with characteristic elevation of serum glucose levels at an advanced age. Glucose and insulin tolerance tests revealed that the increased blood glucose in Insl5(-/-) mice was due to glucose intolerance resulting from reduced insulin secretion. Morphometric and immunohistological analyses revealed that the Insl5(-/-) mice had markedly reduced average islets area and β-cell numbers. Furthermore, immunohistochemistry showed the expression of INSL5 in enteroendocrine cells in the colorectal epithelium and the presence of its putative receptor relaxin family peptide receptor 4 in pancreatic islet cells. These results suggest the potential role of INSL5 signaling in the regulation of insulin secretion and β-cell homeostasis. 相似文献
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Meunier L Siddeek B Vega A Lakhdari N Inoubli L Bellon RP Lemaire G Mauduit C Benahmed M 《Endocrinology》2012,153(4):1936-1947
945.
A Brautbar LA Pompeii A Dehghan JS Ngwa V Nambi SS Virani F Rivadeneira AG Uitterlinden A Hofman JC Witteman MJ Pencina AR Folsom LA Cupples CM Ballantyne E Boerwinkle 《Atherosclerosis》2012,223(2):421-426
ObjectiveMultiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs).MethodsSNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS.ResultsThe GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07–1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ = 0.007; 95% CI, 0.004–0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10–1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02–1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest.ConclusionAddition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies. 相似文献
946.
Krone N Reisch N Idkowiak J Dhir V Ivison HE Hughes BA Rose IT O'Neil DM Vijzelaar R Smith MJ MacDonald F Cole TR Adolphs N Barton JS Blair EM Braddock SR Collins F Cragun DL Dattani MT Day R Dougan S Feist M Gottschalk ME Gregory JW Haim M Harrison R Olney AH Hauffa BP Hindmarsh PC Hopkin RJ Jira PE Kempers M Kerstens MN Khalifa MM Köhler B Maiter D Nielsen S O'Riordan SM Roth CL Shane KP Silink M Stikkelbroeck NM Sweeney E Szarras-Czapnik M Waterson JR Williamson L Hartmann MF Taylor NF 《The Journal of clinical endocrinology and metabolism》2012,97(2):E257-E267
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948.
Pillai SK Abdel-Mohsen M Guatelli J Skasko M Monto A Fujimoto K Yukl S Greene WC Kovari H Rauch A Fellay J Battegay M Hirschel B Witteck A Bernasconi E Ledergerber B Günthard HF Wong JK;Swiss HIV Cohort Study 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(8):3035-3040
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