ArticleThe Journal of biological chemistry2018
Islet proteomics reveals genetic variation in dopamine production resulting in altered insulin secretion.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Dopaminergic modulation of pancreatic beta-cell insulin secretion and implications for antipsychotic-induced glucose dysregulation: a systematic review and meta-analysis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Pooled it
- Structural and functional impact of cystic fibrosis on endocrine pancreatic innervation.Clinical science (London, England : 1979) · 2026Article
- Multi-tissue multi-omics integration reveals tissue-specific pathways, gene networks and drug candidates for type 1 diabetes.Diabetologia · 2026Article
- Proinsulin regulators identified with CRISPR screen and in vivo mouse QTL mapping.Nature communications · 2026Article
- 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
- Decoding adult murine pancreatic islet cell diversity through cell type-resolved proteomics and phosphoproteomics.Communications biology · 2025Article
- Genetics and diet shape the relationship between islet function and whole body metabolism.American journal of physiology. Endocrinology and metabolism · 2024Article
- Molecular mechanism responsible for sex differences in electrical activity of mouse pancreatic β cells.JCI insight · 2024Article
- KThe Journal of physiology · 2023Article
- 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
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- Article
- Roles of Pancreatic Islet Catecholamine Neurotransmitters in Glycemic Control and in Antipsychotic Drug-Induced Dysglycemia.Diabetes · 2023Review
- Article
- Metabolic cycles and signals for insulin secretion.Cell metabolism · 2022Review
- β Cell-specific deletion of Zfp148 improves nutrient-stimulated β cell Ca2+ responses.JCI insight · 2022Article
- Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.Antioxidants & redox signaling · 2022Review
- Diabetes mellitus and Parkinson's disease: dangerous liaisons between insulin and dopamine.Neural regeneration research · 2022Review
- It's What and When You Eat: An Overview of Transcriptional and Epigenetic Responses to Dietary Perturbations in Pancreatic Islets.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The mouse is a critical model in diabetes research, but most research in mice has been limited to a small number of mouse strains and limited genetic variation. Using the eight founder strains and both sexes of the Collaborative Cross (C57BL/6J (B6), A/J, 129S1/SvImJ (129), NOD/ShiLtJ (NOD), NZO/HILtJ (NZO), PWK/PhJ (PWK), WSB/EiJ (WSB), and CAST/EiJ (CAST)), we investigated the genetic dependence of diabetes-related metabolic phenotypes and insulin secretion. We found that strain background is associated with an extraordinary range in body weight, plasma glucose, insulin, triglycerides, and insulin secretion. Our whole-islet proteomic analysis of the eight mouse strains demonstrates that genetic background exerts a strong influence on the islet proteome that can be linked to the differences in diabetes-related metabolic phenotypes and insulin secretion. We computed protein modules consisting of highly correlated proteins that enrich for biological pathways and provide a searchable database of the islet protein expression profiles. To validate the data resource, we identified tyrosine hydroxylase (Th), a key enzyme in catecholamine synthesis, as a protein that is highly expressed in β-cells of PWK and CAST islets. We show that CAST islets synthesize elevated levels of dopamine, which suppresses insulin secretion. Prior studies, using only the B6 strain, concluded that adult mouse islets do not synthesize l-3,4-dihydroxyphenylalanine (l-DOPA), the product of Th and precursor of dopamine. Thus, the choice of the CAST strain, guided by our islet proteomic survey, was crucial for these discoveries. In summary, we provide a valuable data resource to the research community, and show that proteomic analysis identified a strain-specific pathway by which dopamine synthesized in β-cells inhibits insulin secretion.
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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.