ArticlePloS one2013
RNAi screening in primary human hepatocytes of genes implicated in genome-wide association studies for roles in type 2 diabetes identifies roles for CAMK1D and CDKAL1, among others, in hepatic glucose regulation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes.Nature communications · 2016Pooled it
- Integrated Genomic-Metabolomic Analysis for Tri-Categorical Classification of Type 2 Diabetes Status in the Korean Ansan-Ansung Cohort.International journal of molecular sciences · 2025Article
- Podocyte-specific KLF6 primes proximal tubule CaMK1D signaling to attenuate diabetic kidney disease.Nature communications · 2024Article
- CaMK1D signalling in AgRP neurons promotes ghrelin-mediated food intake.Nature metabolism · 2023Article
- TRIM21 ameliorates hepatic glucose and lipid metabolic disorders in type 2 diabetes mellitus by ubiquitination of PEPCK1 and FASN.Cellular and molecular life sciences : CMLS · 2023Article
- Backbone resonance assignments of the catalytic and regulatory domains of CaBiomolecular NMR assignments · 2020Article
- Transcriptome-wide analysis of PGC-1α-binding RNAs identifies genes linked to glucagon metabolic action.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Discovery of Highly Selective Inhibitors of Calmodulin-Dependent Kinases That Restore Insulin Sensitivity in the Diet-Induced ObesityJournal of medicinal chemistry · 2020Article
- An integrated investigation of oocyte developmental competence: expression of key genes in human cumulus cells, morphokinetics of early divisions, blastulation, and euploidy.Journal of assisted reproduction and genetics · 2019Article
- Genetic Variants Associated With Obesity and Insulin Resistance in Hispanic Boys With Nonalcoholic Fatty Liver Disease.Journal of pediatric gastroenterology and nutrition · 2018Article
- Contribution of independent and pleiotropic genetic effects in the metabolic syndrome in a hypertensive rat.PloS one · 2017Article
- Maternal Obesity in Pregnancy Developmentally Programs Adipose Tissue Inflammation in Young, Lean Male Mice Offspring.Endocrinology · 2016Article
- Identification of a regulatory variant that binds FOXA1 and FOXA2 at the CDC123/CAMK1D type 2 diabetes GWAS locus.PLoS genetics · 2014Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association (GWA) studies have described a large number of new candidate genes that contribute to of Type 2 Diabetes (T2D). In some cases, small clusters of genes are implicated, rather than a single gene, and in all cases, the genetic contribution is not defined through the effects on a specific organ, such as the pancreas or liver. There is a significant need to develop and use human cell-based models to examine the effects these genes may have on glucose regulation. We describe the development of a primary human hepatocyte model that adjusts glucose disposition according to hormonal signals. This model was used to determine whether candidate genes identified in GWA studies regulate hepatic glucose disposition through siRNAs corresponding to the list of identified genes. We find that several genes affect the storage of glucose as glycogen (glycolytic response) and/or affect the utilization of pyruvate, the critical step in gluconeogenesis. Of the genes that affect both of these processes, CAMK1D, TSPAN8 and KIF11 affect the localization of a mediator of both gluconeogenesis and glycolysis regulation, CRTC2, to the nucleus in response to glucagon. In addition, the gene CDKAL1 was observed to affect glycogen storage, and molecular experiments using mutant forms of CDK5, a putative target of CDKAL1, in HepG2 cells show that this is mediated by coordinate regulation of CDK5 and PKA on MEK, which ultimately regulates the phosphorylation of ribosomal protein S6, a critical step in the insulin signaling pathway.
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