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Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease

Population level variation and molecular mechanisms behind insulin secretion in response to carbohydrate, protein, and fat remain uncharacterized despite ramifications for personalized nutrition. We now define prototypical insulin secretion dynamics in response to the three macronutrients in islets from 140 cadaveric donors, including those diagnosed with type 2 diabetes. We leverage the insulin response heterogeneity and use transcriptomics and proteomics to identify molecular pathways of specific nutrient responsiveness. Surprisingly, we find robust insulin secretion to fatty acid stimulus in ~8% of donors, challenging the idea that fat has negligible effects on insulin release. Distinct islet proteomes with differences in metabolic signalling networks convey this hyper-responsiveness to fat relative to carbohydrate. By comparing human islets to human embryonic stem cell-derived islet clusters, we show that, unlike glucose-responsiveness, fat hyper-responsiveness is equivalent and may be a hallmark of functionally immature cells. Our study represents the first comparison of dynamic responses to nutrients and multi-omics analysis in human insulin secreting cells. Responses of different people’s islets to carbohydrate, protein, and fat lay the groundwork for personalized nutrition.

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Data Access Policy of the Datasets from the Translational Genomics of Diabetes Lab at Stanford University

DATA ACCESS AGREEMENT This agreement governs the terms on which access will be granted to the RNA sequencing data generated as part of the CALCOCO2 study. In signing this agreement, You are agreeing to be bound by the terms and conditions of access set out in this agreement. For the sake of clarity, the terms of access set out in this agreement apply both to the User and the User’s Institution (as defined below). User Institution and User are referred to within the agreement as “You” and “Your” shall be construed accordingly. Definitions: Investigators means the group of investigators based in Stanford, US and Oxford, UK which have generated the Data. Data means all and any human genetic data obtained from the Investigators. Data Subject means a person, who has been informed of the purpose for which the Data is held and has given his/her informed consent thereto. User means a researcher whose User Institution has previously completed this Data Access Agreement and has received acknowledgement of its acceptance. Publications means, without limitation, articles published in print journals, electronic journals, reviews, books, posters and other written and verbal presentations of research. User Institution means the organization at which the User is employed, affiliated or enrolled. Terms and Conditions: In signing this Agreement: 1. You agree to use the Data only for the advancement of medical research, according to the consent obtained from sample donors. 2. You agree not to use the Data or any part thereof for the creation of products for sale or for any commercial purpose. 3. You agree to preserve, at all times, the confidentiality of information and Data pertaining to Data Subjects. In particular, You undertake not to use, or attempt to use the Data to compromise or otherwise infringe the confidentiality of information on Data Subjects and their right to privacy. 4. You agree not to attempt to link the data provided under this agreement to other information or archive data available for the data sets provided, even if access to that data has been formally granted to you, or it is freely available without restriction, without specific permission being sought from the relevant access committees. 5. You agree not to transfer or disclose the Data, in whole or part, or any identifiable material derived from the Data, to others, except as necessary for data/safety monitoring or programme management. Should You wish to share the Data with a collaborator outside the same Institution, the third party must make a separate application for access to the Data. 6. You agree to use the data for the approved purpose and project described in your application; use of the data for a new purpose or project will require a new application and approval. 7. You agree to acknowledge in any work based in whole or part on the Data, the published paper from which the Data derives. 8. You accept that the Investigators, the original data creators, depositors or copyright holders, or the funders of the Data or any part of the Data supplied: a. bear no legal responsibility for the accuracy or comprehensiveness of the Data; and b. accept no liability for indirect, consequential, or incidental, damages or losses arising from use of the Data, or from the unavailability of, or break in access to, the Data for whatever reason. 9. You understand and acknowledge that the Data is protected by copyright and other intellectual property rights, and that duplication, except as reasonably required to carry out Your research with the Data, or sale of all or part of the Data on any media is not permitted. 10. You recognise that nothing in this agreement shall operate to transfer to the User Institution any intellectual property rights relating to the Data. The User Institution has the right to develop intellectual property based on comparisons with their own data. 11. You accept that this agreement will terminate immediately upon any breach of this agreement by You and You will be required to destroy any Data held. 12. You accept that it may be necessary for the Investigators or its appointed agent to alter the terms of this agreement from time to time in order to address new concerns. In this event, the Investigators or its appointed agent will contact You to inform You of any changes and You agree that Your continued use of the Data shall be dependent on the parties entering into a new version of the Agreement. 13. You accept that the Data is protected by and subject to international laws and that You are responsible for ensuring compliance with any such applicable law. The Translational Genomics of Diabetes Lab Data Access Committee reserves the right to request and inspect data security and management documentation to ensure the adequacy of data protection measures in countries that have no national laws comparable to that which pertain in the EAA. 14. This agreement shall be construed, interpreted and governed by the laws of US and UK and shall be subject to the non-exclusive jurisdiction of the US and UK courts.

Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
EGAS00001007241 RNASeq

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Quality Report
Located in
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EGAF00008072482 fq.gz 143.8 MB Report
EGAF00008072483 fq.gz 139.4 MB Report
EGAF00008072484 fq.gz 148.1 MB Report
EGAF00008072485 fq.gz 140.2 MB Report
EGAF00008072486 fq.gz 146.7 MB Report
EGAF00008072487 fq.gz 140.4 MB Report
EGAF00008072488 fq.gz 146.5 MB Report
EGAF00008072489 fq.gz 137.7 MB Report
EGAF00008072490 fq.gz 145.0 MB Report
EGAF00008072491 fq.gz 137.5 MB Report
EGAF00008072492 fq.gz 151.6 MB Report
EGAF00008072493 fq.gz 138.4 MB Report
EGAF00008072494 fq.gz 151.8 MB Report
EGAF00008072495 fq.gz 138.0 MB Report
EGAF00008072496 fq.gz 149.7 MB Report
EGAF00008072497 fq.gz 139.1 MB Report
EGAF00008072498 fq.gz 148.0 MB Report
EGAF00008072499 fq.gz 138.9 MB Report
EGAF00008072500 fq.gz 145.2 MB Report
EGAF00008072501 fq.gz 138.0 MB Report
EGAF00008072502 fq.gz 143.1 MB Report
EGAF00008072503 fq.gz 138.6 MB Report
EGAF00008072504 fq.gz 142.5 MB Report
EGAF00008072505 fq.gz 139.3 MB Report
EGAF00008072506 fq.gz 142.7 MB Report
EGAF00008072507 fq.gz 150.9 MB Report
EGAF00008072508 fq.gz 157.4 MB Report
EGAF00008072509 fq.gz 151.9 MB Report
EGAF00008072510 fq.gz 163.2 MB Report
EGAF00008072511 fq.gz 152.7 MB Report
EGAF00008072512 fq.gz 161.7 MB Report
EGAF00008072513 fq.gz 152.6 MB Report
EGAF00008072514 fq.gz 161.2 MB Report
EGAF00008072515 fq.gz 148.9 MB Report
EGAF00008072516 fq.gz 158.9 MB Report
EGAF00008072517 fq.gz 150.0 MB Report
EGAF00008072518 fq.gz 167.6 MB Report
EGAF00008072519 fq.gz 150.6 MB Report
EGAF00008072520 fq.gz 167.5 MB Report
EGAF00008072521 fq.gz 150.4 MB Report
EGAF00008072522 fq.gz 165.7 MB Report
EGAF00008072523 fq.gz 151.6 MB Report
EGAF00008072524 fq.gz 163.8 MB Report
EGAF00008072525 fq.gz 151.2 MB Report
EGAF00008072526 fq.gz 160.3 MB Report
EGAF00008072527 fq.gz 150.3 MB Report
EGAF00008072528 fq.gz 156.2 MB Report
EGAF00008072529 fq.gz 151.1 MB Report
EGAF00008072530 fq.gz 156.0 MB Report
EGAF00008072531 fq.gz 152.0 MB Report
EGAF00008072532 fq.gz 156.4 MB Report
EGAF00008072533 fq.gz 153.4 MB Report
EGAF00008072534 fq.gz 157.5 MB Report
EGAF00008072535 fq.gz 153.3 MB Report
EGAF00008072536 fq.gz 161.7 MB Report
EGAF00008072537 fq.gz 154.1 MB Report
EGAF00008072538 fq.gz 160.2 MB Report
EGAF00008072539 fq.gz 154.2 MB Report
EGAF00008072540 fq.gz 159.7 MB Report
EGAF00008072541 fq.gz 151.3 MB Report
EGAF00008072542 fq.gz 158.2 MB Report
EGAF00008072543 fq.gz 151.4 MB Report
EGAF00008072544 fq.gz 165.7 MB Report
EGAF00008072545 fq.gz 152.1 MB Report
EGAF00008072546 fq.gz 165.6 MB Report
EGAF00008072547 fq.gz 152.0 MB Report
EGAF00008072548 fq.gz 163.6 MB Report
EGAF00008072549 fq.gz 153.2 MB Report
EGAF00008072550 fq.gz 161.7 MB Report
EGAF00008072551 fq.gz 152.8 MB Report
EGAF00008072552 fq.gz 158.5 MB Report
EGAF00008072553 fq.gz 152.5 MB Report
EGAF00008072554 fq.gz 156.9 MB Report
EGAF00008072555 fq.gz 153.4 MB Report
EGAF00008072556 fq.gz 156.5 MB Report
EGAF00008072557 fq.gz 154.2 MB Report
EGAF00008072558 fq.gz 156.7 MB Report
EGAF00008072559 fq.gz 151.5 MB Report
EGAF00008072560 fq.gz 155.1 MB Report
EGAF00008072561 fq.gz 151.9 MB Report
EGAF00008072562 fq.gz 159.7 MB Report
EGAF00008072563 fq.gz 152.4 MB Report
EGAF00008072564 fq.gz 158.0 MB Report
EGAF00008072565 fq.gz 152.5 MB Report
EGAF00008072566 fq.gz 157.6 MB Report
EGAF00008072567 fq.gz 149.3 MB Report
EGAF00008072568 fq.gz 155.7 MB Report
EGAF00008072569 fq.gz 149.8 MB Report
EGAF00008072570 fq.gz 163.3 MB Report
EGAF00008072571 fq.gz 150.8 MB Report
EGAF00008072572 fq.gz 163.6 MB Report
EGAF00008072573 fq.gz 150.3 MB Report
EGAF00008072574 fq.gz 161.4 MB Report
EGAF00008072575 fq.gz 151.4 MB Report
EGAF00008072576 fq.gz 159.4 MB Report
EGAF00008072577 fq.gz 151.0 MB Report
EGAF00008072578 fq.gz 156.2 MB Report
EGAF00008072579 fq.gz 149.8 MB Report
EGAF00008072580 fq.gz 153.6 MB Report
EGAF00008072581 fq.gz 150.4 MB Report
EGAF00008072582 fq.gz 153.0 MB Report
EGAF00008072583 fq.gz 151.5 MB Report
EGAF00008072584 fq.gz 153.6 MB Report
EGAF00008072585 fq.gz 159.6 MB Report
EGAF00008072586 fq.gz 166.4 MB Report
EGAF00008072587 fq.gz 159.0 MB Report
EGAF00008072588 fq.gz 169.9 MB Report
EGAF00008072589 fq.gz 159.8 MB Report
EGAF00008072590 fq.gz 168.3 MB Report
EGAF00008072591 fq.gz 159.7 MB Report
EGAF00008072592 fq.gz 167.6 MB Report
EGAF00008072593 fq.gz 156.9 MB Report
EGAF00008072594 fq.gz 166.2 MB Report
EGAF00008072595 fq.gz 157.6 MB Report
EGAF00008072596 fq.gz 174.6 MB Report
EGAF00008072597 fq.gz 158.2 MB Report
EGAF00008072598 fq.gz 174.5 MB Report
EGAF00008072599 fq.gz 157.9 MB Report
EGAF00008072600 fq.gz 172.3 MB Report
EGAF00008072601 fq.gz 158.7 MB Report
EGAF00008072602 fq.gz 169.9 MB Report
EGAF00008072603 fq.gz 158.6 MB Report
EGAF00008072604 fq.gz 166.9 MB Report
EGAF00008072605 fq.gz 157.5 MB Report
EGAF00008072606 fq.gz 164.3 MB Report
EGAF00008072607 fq.gz 158.1 MB Report
EGAF00008072608 fq.gz 163.7 MB Report
EGAF00008072609 fq.gz 159.1 MB Report
EGAF00008072610 fq.gz 164.1 MB Report
EGAF00008072611 fq.gz 171.2 MB Report
EGAF00008072612 fq.gz 177.5 MB Report
EGAF00008072613 fq.gz 171.0 MB Report
EGAF00008072614 fq.gz 182.5 MB Report
EGAF00008072615 fq.gz 172.3 MB Report
EGAF00008072616 fq.gz 181.0 MB Report
EGAF00008072617 fq.gz 172.5 MB Report
EGAF00008072618 fq.gz 180.4 MB Report
EGAF00008072619 fq.gz 169.0 MB Report
EGAF00008072620 fq.gz 178.4 MB Report
EGAF00008072621 fq.gz 169.9 MB Report
EGAF00008072622 fq.gz 188.5 MB Report
EGAF00008072623 fq.gz 171.0 MB Report
EGAF00008072624 fq.gz 188.7 MB Report
EGAF00008072625 fq.gz 170.8 MB Report
EGAF00008072626 fq.gz 186.4 MB Report
EGAF00008072627 fq.gz 171.9 MB Report
EGAF00008072628 fq.gz 183.9 MB Report
EGAF00008072629 fq.gz 171.9 MB Report
EGAF00008072630 fq.gz 180.5 MB Report
EGAF00008072631 fq.gz 168.6 MB Report
EGAF00008072632 fq.gz 175.1 MB Report
EGAF00008072633 fq.gz 169.2 MB Report
EGAF00008072634 fq.gz 174.3 MB Report
EGAF00008072635 fq.gz 170.3 MB Report
EGAF00008072636 fq.gz 174.6 MB Report
EGAF00008072637 fq.gz 155.7 MB Report
EGAF00008072638 fq.gz 162.1 MB Report
EGAF00008072639 fq.gz 156.1 MB Report
EGAF00008072640 fq.gz 167.1 MB Report
EGAF00008072641 fq.gz 156.9 MB Report
EGAF00008072642 fq.gz 165.6 MB Report
EGAF00008072643 fq.gz 156.9 MB Report
EGAF00008072644 fq.gz 164.8 MB Report
EGAF00008072645 fq.gz 153.8 MB Report
EGAF00008072646 fq.gz 163.0 MB Report
EGAF00008072647 fq.gz 154.7 MB Report
EGAF00008072648 fq.gz 171.8 MB Report
EGAF00008072649 fq.gz 155.7 MB Report
EGAF00008072650 fq.gz 172.0 MB Report
EGAF00008072651 fq.gz 155.2 MB Report
EGAF00008072652 fq.gz 169.8 MB Report
EGAF00008072653 fq.gz 156.4 MB Report
EGAF00008072654 fq.gz 168.0 MB Report
EGAF00008072655 fq.gz 156.0 MB Report
EGAF00008072656 fq.gz 164.5 MB Report
EGAF00008072657 fq.gz 154.4 MB Report
EGAF00008072658 fq.gz 161.3 MB Report
EGAF00008072659 fq.gz 155.0 MB Report
EGAF00008072660 fq.gz 160.6 MB Report
EGAF00008072661 fq.gz 156.0 MB Report
EGAF00008072662 fq.gz 161.0 MB Report
EGAF00008072663 fq.gz 137.6 MB Report
EGAF00008072664 fq.gz 142.5 MB Report
EGAF00008072665 fq.gz 137.5 MB Report
EGAF00008072666 fq.gz 146.5 MB Report
EGAF00008072667 fq.gz 138.3 MB Report
EGAF00008072668 fq.gz 145.1 MB Report
EGAF00008072669 fq.gz 138.3 MB Report
EGAF00008072670 fq.gz 144.6 MB Report
EGAF00008072671 fq.gz 135.8 MB Report
EGAF00008072672 fq.gz 143.3 MB Report
EGAF00008072673 fq.gz 136.0 MB Report
EGAF00008072674 fq.gz 150.4 MB Report
EGAF00008072675 fq.gz 136.7 MB Report
EGAF00008072676 fq.gz 150.4 MB Report
EGAF00008072677 fq.gz 136.3 MB Report
EGAF00008072678 fq.gz 148.2 MB Report
EGAF00008072679 fq.gz 137.3 MB Report
EGAF00008072680 fq.gz 146.5 MB Report
EGAF00008072681 fq.gz 137.3 MB Report
EGAF00008072682 fq.gz 144.0 MB Report
EGAF00008072683 fq.gz 136.6 MB Report
EGAF00008072684 fq.gz 141.8 MB Report
EGAF00008072685 fq.gz 136.9 MB Report
EGAF00008072686 fq.gz 140.9 MB Report
EGAF00008072687 fq.gz 137.9 MB Report
EGAF00008072688 fq.gz 141.3 MB Report
EGAF00008072689 fq.gz 458.9 MB Report
EGAF00008072690 fq.gz 503.9 MB Report
EGAF00008072691 fq.gz 461.5 MB Report
EGAF00008072692 fq.gz 481.4 MB Report
EGAF00008072693 fq.gz 451.5 MB Report
EGAF00008072694 fq.gz 472.3 MB Report
EGAF00008072695 fq.gz 453.3 MB Report
EGAF00008072696 fq.gz 504.9 MB Report
EGAF00008072697 fq.gz 429.1 MB Report
EGAF00008072698 fq.gz 470.5 MB Report
EGAF00008072699 fq.gz 434.3 MB Report
EGAF00008072700 fq.gz 469.3 MB Report
EGAF00008072701 fq.gz 447.7 MB Report
EGAF00008072702 fq.gz 488.1 MB Report
EGAF00008072703 fq.gz 157.5 MB Report
EGAF00008072704 fq.gz 164.1 MB Report
EGAF00008072705 fq.gz 156.8 MB Report
EGAF00008072706 fq.gz 167.2 MB Report
EGAF00008072707 fq.gz 157.7 MB Report
EGAF00008072708 fq.gz 165.9 MB Report
EGAF00008072709 fq.gz 157.9 MB Report
EGAF00008072710 fq.gz 165.5 MB Report
EGAF00008072711 fq.gz 154.7 MB Report
EGAF00008072712 fq.gz 163.6 MB Report
EGAF00008072713 fq.gz 156.4 MB Report
EGAF00008072714 fq.gz 173.3 MB Report
EGAF00008072715 fq.gz 157.3 MB Report
EGAF00008072716 fq.gz 173.5 MB Report
EGAF00008072717 fq.gz 157.0 MB Report
EGAF00008072718 fq.gz 171.5 MB Report
EGAF00008072719 fq.gz 158.4 MB Report
EGAF00008072720 fq.gz 169.7 MB Report
EGAF00008072721 fq.gz 158.2 MB Report
EGAF00008072722 fq.gz 166.6 MB Report
EGAF00008072723 fq.gz 155.2 MB Report
EGAF00008072724 fq.gz 161.6 MB Report
EGAF00008072725 fq.gz 156.0 MB Report
EGAF00008072726 fq.gz 161.2 MB Report
EGAF00008072727 fq.gz 157.0 MB Report
EGAF00008072728 fq.gz 161.7 MB Report
EGAF00008072729 fq.gz 361.0 MB Report
EGAF00008072730 fq.gz 397.5 MB Report
EGAF00008072731 fq.gz 363.6 MB Report
EGAF00008072732 fq.gz 380.3 MB Report
EGAF00008072733 fq.gz 356.4 MB Report
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EGAF00008072737 fq.gz 346.0 MB Report
EGAF00008072738 fq.gz 381.1 MB Report
EGAF00008072739 fq.gz 345.9 MB Report
EGAF00008072740 fq.gz 375.1 MB Report
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EGAF00008072742 fq.gz 382.2 MB Report
EGAF00008072743 fq.gz 430.9 MB Report
EGAF00008072744 fq.gz 471.8 MB Report
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EGAF00008072750 fq.gz 471.5 MB Report
EGAF00008072751 fq.gz 411.9 MB Report
EGAF00008072752 fq.gz 450.3 MB Report
EGAF00008072753 fq.gz 415.2 MB Report
EGAF00008072754 fq.gz 446.9 MB Report
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EGAF00008072756 fq.gz 457.1 MB Report
EGAF00008072757 fq.gz 378.7 MB Report
EGAF00008072758 fq.gz 414.2 MB Report
EGAF00008072759 fq.gz 384.3 MB Report
EGAF00008072760 fq.gz 398.9 MB Report
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EGAF00008072763 fq.gz 376.2 MB Report
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EGAF00008072765 fq.gz 360.9 MB Report
EGAF00008072766 fq.gz 394.9 MB Report
EGAF00008072767 fq.gz 362.9 MB Report
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EGAF00008072769 fq.gz 368.2 MB Report
EGAF00008072770 fq.gz 399.8 MB Report
EGAF00008072771 fq.gz 359.4 MB Report
EGAF00008072772 fq.gz 393.5 MB Report
EGAF00008072773 fq.gz 364.8 MB Report
EGAF00008072774 fq.gz 380.5 MB Report
EGAF00008072775 fq.gz 357.2 MB Report
EGAF00008072776 fq.gz 373.8 MB Report
EGAF00008072777 fq.gz 347.7 MB Report
EGAF00008072778 fq.gz 386.6 MB Report
EGAF00008072779 fq.gz 343.6 MB Report
EGAF00008072780 fq.gz 379.7 MB Report
EGAF00008072781 fq.gz 346.4 MB Report
EGAF00008072782 fq.gz 376.5 MB Report
EGAF00008072783 fq.gz 355.0 MB Report
EGAF00008072784 fq.gz 389.4 MB Report
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EGAF00008072806 fq.gz 482.8 MB Report
EGAF00008072807 fq.gz 449.7 MB Report
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EGAF00008072811 fq.gz 511.7 MB Report
EGAF00008072812 fq.gz 544.4 MB Report
EGAF00008072813 fq.gz 511.6 MB Report
EGAF00008072814 fq.gz 560.5 MB Report
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EGAF00008072816 fq.gz 563.3 MB Report
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590 Files (353.1 GB)