ArticleThe Journal of clinical investigation2019
Gene loci associated with insulin secretion in islets from non-diabetic mice.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 88 citations in OpenAlex.
- A panel of Diversity Outbred mouse embryonic stem cells: enabling the functional characterization of natural genetic variationbioRxiv : the preprint server for biology · 2026Article
- Genetic architecture of the murine serum metabolome reveals carboxyl esterases as master regulators of circulating fatty acid metabolism.bioRxiv : the preprint server for biology · 2026Article
- Distinct genetic architecture of gene and isoform level QTL in the Diversity Outbred (DO) mouse population.bioRxiv : the preprint server for biology · 2026Article
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- Simplifying Systems Genetics with QTLretrievR: An R Package for Molecular QTL Identification.bioRxiv : the preprint server for biology · 2026Article
- Synteny - a high throughput web tool to streamline causal gene prioritisation and provide insight into protein function.Scientific reports · 2025Article
- From Human to Mouse and Back Again: Genetic and Genomic Ta(i)les of Islet Dysfunction in Type 2 Diabetes.Annual review of genetics · 2025Review
- Genetics-nutrition interactions control diurnal enhancer-promoter dynamics and liver lipid metabolism.Cell metabolism · 2025Article
- Modulating hormonally upregulated neu-associated kinase (HUNK) activity in breast cancer: The development of HUNK inhibitors.The Journal of pharmacology and experimental therapeutics · 2025Review
- Transcripts with high distal heritability mediate genetic effects on complex metabolic traits.Nature communications · 2025Article
- Sphingolipid metabolism-related genes for the diagnosis of metabolic syndrome by integrated bioinformatics analysis and Mendelian randomization identification.Diabetology & metabolic syndrome · 2025Article
- Unlocking metabolic insights with mouse genetic diversity.The EMBO journal · 2024Article
- Improving the predictive power of mouse models.Nature biotechnology · 2024Article
- The metabolic consequences of 'yo-yo' dieting are markedly influenced by genetic diversity.International journal of obesity (2005) · 2024Article
- Spontaneous Akt2 deficiency in a colony of NOD mice exhibiting early diabetes.Scientific reports · 2024Article
- Genetic variation is a key determinant of chromatin accessibility and drives differences in the regulatory landscape of C57BL/6J and 129S1/SvImJ mice.Nucleic acids research · 2024Article
- Article
- Identification of genetic drivers of plasma lipoprotein size in the Diversity Outbred mouse population.Journal of lipid research · 2023Article
- Systems genetics approaches for understanding complex traits with relevance for human disease.eLife · 2023Review
- Article
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18 authors at 4 institutions in 2 countries.
Funding
Abstract
Genetic susceptibility to type 2 diabetes is primarily due to β-cell dysfunction. However, a genetic study to directly interrogate β-cell function ex vivo has never been previously performed. We isolated 233,447 islets from 483 Diversity Outbred (DO) mice maintained on a Western-style diet, and measured insulin secretion in response to a variety of secretagogues. Insulin secretion from DO islets ranged >1,000-fold even though none of the mice were diabetic. The insulin secretory response to each secretagogue had a unique genetic architecture; some of the loci were specific for one condition, whereas others overlapped. Human loci that are syntenic to many of the insulin secretion QTL from mouse are associated with diabetes-related SNPs in human genome-wide association studies. We report on three genes, Ptpn18, Hunk and Zfp148, where the phenotype predictions from the genetic screen were fulfilled in our studies of transgenic mouse models. These three genes encode a non-receptor type protein tyrosine phosphatase, a serine/threonine protein kinase, and a Krϋppel-type zinc-finger transcription factor, respectively. Our results demonstrate that genetic variation in insulin secretion that can lead to type 2 diabetes is discoverable in non-diabetic individuals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.