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Hyperinsulinemia is the earliest symptom of insulin resistance (IR), but a causal relationship between the two remains to be established. Here we show that a protein kinase D2 (PRKD2) nonsense mutation (K410X) in two rhesus monkeys with extreme hyperinsulinemia along with IR and metabolic defects by using extreme phenotype sampling and deep sequencing analyses. This mutation reduces PRKD2 at both the mRNA and the protein levels. Taking advantage of a PRKD2-KO mouse model, we demonstrate that PRKD2 deletion triggers hyperinsulinemia which precedes to IR and metabolic disorders in the PRKD2 ablation mice. PRKD2 deficiency promotes β-cell insulin secretion by increasing the expression and activity of L-type Ca2+ channels and subsequently augmenting high glucose- and membrane depolarization-induced Ca2+ influx. Altogether, these results indicate that down-regulation of PRKD2 is involved in the pathogenesis of hyperinsulinemia which, in turn, results in IR and metabolic disorders.
Pubmed ID: 29789568
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Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsCommercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
View all literature mentionsThe directing and coordinating authority responsible for public health within the United Nations system. The WHO Regional Office for Europe (WHO/Europe) is one of the six regional offices around the world. It serves the WHO European Region, which comprises 53 countries from the Atlantic to the Pacific oceans. WHO/Europe collaborates with a range of public health stakeholders in the Region and globally, to ensure that coordinated action is taken to develop and implement efficient health policies and to strengthen health systems. WHO/Europe is made up of public health, scientific, and technical experts.
View all literature mentionsGenetic variant annotation and effect prediction software toolbox that annotates and predicts effects of variants on genes (such as amino acid changes). By using standards, such as VCF, SnpEff makes it easy to integrate with other programs.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.
View all literature mentionsCompany provides laboratories worldwide with analytical instruments and supplies, clinical and diagnostic testing services, consumables, applications and expertise in life sciences and applied chemical markets.
View all literature mentionsSoftware used for Bio-Rad imaging systems to acquire, quantitate, and analyze a variety of data. The software allows automatic configuration of imaging systems with appropriate filters, lasers, LEDs, and other illumination sources. It also contains tools for automated analysis of tests and assays such as 1-D electrophoretic gels, western blots, and colony counts.
View all literature mentionsCell line INS-1 is a Cancer cell line with a species of origin Rattus norvegicus (Rat)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line Hepa 1-6 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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