Biomarkers for precision therapy and prevention of type 2 diabetes

Mini-symposium

10 March 2020
Scania University Hospital, Malmö

Assessing risk and progression of pre-diabetes and type 2 diabetes to enable disease modification

The stated goal of RHAPSODY is to define a molecular taxonomy of type 2 diabetes mellitus (T2D) that will support patient segmentation, inform clinical trial design, and the establishment of regulatory paths for the adoption of novel strategies for diabetes prevention and treatment.

Our plans are built upon:

access to large European cohorts with comprehensive genetic analyses, rich longitudinal clinical, biochemical data and samples
detailed multi-omic maps of key T2D-relevant tissues and organs
large expertise in the development and use of novel genetic, epigenetic, biochemical and physiological experimental approaches
the ability to combine existing and novel data sets through effective data federation and use of these datasets in systems biology approaches towards precision medicine;
expertise in regulatory approval, health economics and patient engagement.

These activities will lead to the discovery of novel biomarkers for improved T2D taxonomy, to support development of pharmaceutical activities, and for use in precision medicine to improve health in Europe and worldwide.

Most recent publications

See all publications

Dragan, I., Sparso, T., Kuznetsov, D., Slieker, R. & Ibberson, M.

dsSwissKnife: An R package for federated data analysis.

bioRxiv 2020.11.17.386813 (2020). doi:10.1101/2020.11.17.386813

Wagner, R., Jaghutriz, B. A., Gerst, F., Barroso Oquendo, M., Machann, J., Schick, F., Löffler, M. W., Nadalin, S., Fend, F., Königsrainer, A., Peter, A., Siegel-Axel, D., Ullrich, S., Häring, H.-U., Fritsche, A. & Heni, M.

Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.

The Journal of Clinical Endocrinology & Metabolism 105, dgaa435 (2020). doi:10.1210/clinem/dgaa435

Hu, M., Cherkaoui, I., Misra, S. & Rutter, G. A.

Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.

Frontiers in Endocrinology 11, 576632 (2020). doi:10.3389/fendo.2020.576632

Muniangi-Muhitu, H., Akalestou, E., Salem, V., Misra, S., Oliver, N. S. & Rutter, G. A.

Covid-19 and Diabetes: A Complex Bidirectional Relationship.

Frontiers in Endocrinology 11, 582936 (2020). doi:10.3389/fendo.2020.582936

Jennings, R. E., Scharfmann, R. & Staels, W.

Transcription factors that shape the mammalian pancreas.

Diabetologia 63, 1974–1980 (2020). doi:10.1007/s00125-020-05161-0

Leal, J., Reed, S. D., Patel, R., Rivero-Arias, O., Li, Y., Schulman, K. A., Califf, R. M., Holman, R. R. & Gray, A. M.

Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data.

Diabetes Care 43, 2485–2492 (2020). doi:10.2337/dc20-0717

Vasiljević, J., Torkko, J. M., Knoch, K.-P. & Solimena, M.

The making of insulin in health and disease.

Diabetologia 63, 1981–1989 (2020). doi:10.1007/s00125-020-05192-7

Si, L., Willis, M. S., Asseburg, C., Nilsson, A., Tew, M., Clarke, P. M., Lamotte, M., Ramos, M., Shao, H., Shi, L., Zhang, P., McEwan, P., Ye, W., Herman, W. H., Kuo, S., Isaman, D. J., Schramm, W., Sailer, F., Brennan, A., Pollard, D., Smolen, H. J., Leal, J., Gray, A., Patel, R., Feenstra, T. & Palmer, A. J.

Evaluating the Ability of Economic Models of Diabetes to Simulate New Cardiovascular Outcomes Trials: A Report on the Ninth Mount Hood Diabetes Challenge.

Value in Health 23, 1163–1170 (2020). doi:10.1016/j.jval.2020.04.1832

Amouyal, C., Castel, J., Guay, C., Lacombe, A., Denom, J., Migrenne-Li, S., Rouault, C., Marquet, F., Georgiadou, E., Stylianides, T., Luquet, S., Le Stunff, H., Scharfmann, R., Clément, K., Rutter, G. A., Taboureau, O., Magnan, C., Regazzi, R. & Andreelli, F.

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice.

EBioMedicine 58, 102895 (2020). doi:10.1016/j.ebiom.2020.102895

10.

Gausserès, B., Liu, J., Foppen, E., Tourrel-Cuzin, C., Rodriguez Sanchez-Archidona, A., Delangre, E., Cruciani-Guglielmacci, C., Pons, S., Maskos, U., Thorens, B., Magnan, C., Movassat, J. & Maouche, K.

The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse.

Biomolecules 10, 1057 (2020). doi:10.3390/biom10071057

11.

Gharavy, S. N. M., Owen, B., Millership, S. J., Chabosseau, P., Pizza, G., Martinez-Sanchez, A., Tasoez, E., Georgiadou, E., Hu, M., Fine, N. H. F., Jacobson, D. A., Dickerson, M., Idevall-Hagren, O., Montoya, A., Kramer, H., Mehta, Z., Withers, D. J., Ninov, N., Gadue, P. J., Cardenas-Diaz, F. L., Cruciani-Guglielmacci, C., Magnan, C., Ibberson, M., Leclerc, I., Voz, M. & Rutter, G. A.

Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis.

bioRxiv 2020.05.18.099200 (2020). doi:10.1101/2020.05.18.099200

12.

Akalestou, E., Suba, K., Lopez-Noriega, L., Georgiadou, E., Chabosseau, P., Leclerc, I., Salem, V. & Rutter, G. A.

Intravital imaging of islet Ca 2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.05.05.078725.

13.

Clough, T. J., Baxan, N., Coakley, E. J., Rivas, C., Zhao, L., Leclerc, I., Martinez-Sanchez, A., Rutter, G. A. & Long, N. J.

Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.

Dalton Transactions 49, 4732–4740 (2020). doi:10.1039/D0DT00332H

14.

Hu, M., Cebola, I., Carrat, G., Jiang, S., Nawaz, S., Khamis, A., Canouil, M., Froguel, P., Schulte, A., Solimena, M., Ibberson, M., Marchetti, P., Cardenas-Diaz, F. L., Gadue, P. J., Hastoy, B., Alemeida-Souza, L., McMahon, H. & Rutter, G. A.

Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a new regulator of insulin secretion.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.31.017707.

15.

Bouland, G. A., Beulens, J. W., Nap, J., van der Slik, A. R., Zaldumbide, A., Hart, L. M. & Slieker, R. C.

Understanding functional consequences of type 2 diabetes risk loci using the universal data integration and visualization R package CONQUER.

(Genomics, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.27.011627.

16.

Carrat, G. R., Haythorne, E., Tomas, A., Haataja, L., Mueller, A., Arvan, P., Piunti, A., Cheng, K., Huang, M., Pullen, T., Georgiadou, E., Stylianides, T., Amirruddin, N. S., Salem, V., Distaso, W., Cakebread, A., Heesom, K. J., Lewis, P. A., Hodson, D., Briant, L. J., Fung, A. C. H., Sessions, R. B., Alpy, F., Kong, A. P. S., Benke, P. I., Torta, F., Teo, A. K. K., Leclerc, I., Solimena, M., Wigley, D. B. & Rutter, G. A.

The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.

bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286

17.

Fang, Z., Chen, S., Pickford, P., Broichhagen, J., Hodson, D. J., Corrêa, I. R., Kumar, S., Görlitz, F., Dunsby, C., French, P., Rutter, G. A., Tan, T., Bloom, S. R., Tomas, A. & Jones, B.

The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.

bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524

18.

Dumayne, C., Tarussio, D., Sanchez-Archidona, A. R., Picard, A., Basco, D., Berney, X. P., Ibberson, M. & Thorens, B.

Klf6 protects β-cells against insulin resistance-induced dedifferentiation.

Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001

19.

Georgiadou, E., Haythorne, E., Dickerson, M. T., Lopez-Noriega, L., Pullen, T. J., da Silva Xavier, G., Davis, S. P. X., Martinez-Sanchez, A., Semplici, F., Rizzuto, R., McGinty, J. A., French, P. M., Cane, M. C., Jacobson, D. A., Leclerc, I. & Rutter, G. A.

The pore-forming subunit MCU of the mitochondrial Ca2+ uniporter is required for normal glucose-stimulated insulin secretion in vitro and in vivo in mice.

Diabetologia 63, 1368–1381 (2020). doi:10.1007/s00125-020-05148-x

20.

Oshima, M., Pechberty, S., Bellini, L., Göpel, S. O., Campana, M., Rouch, C., Dairou, J., Cosentino, C., Fantuzzi, F., Toivonen, S., Marchetti, P., Magnan, C., Cnop, M., Le Stunff, H. & Scharfmann, R.

Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.

Diabetologia 63, 395–409 (2020). doi:10.1007/s00125-019-05046-x

21.

Scharfmann, R., Staels, W. & Albagli, O.

The supply chain of human pancreatic β cell lines.

The Journal of Clinical Investigation 129, 3511–3520 (2019). doi:10.1172/JCI129484

22.

Barovic, M., Distler, M., Schöniger, E., Radisch, N., Aust, D., Weitz, J., Ibberson, M., Schulte, A. M. & Solimena, M.

Metabolically phenotyped pancreatectomized patients as living donors for the study of islets in health and diabetes.

Molecular Metabolism 27, S1-S6 (2019). doi:10.1016/j.molmet.2019.06.006

23.

Canouil, M., Bouland, G. A., Bonnefond, A., Froguel, P., ’t Hart, L. M. & Slieker, R. C.

NACHO: an R package for quality control of NanoString nCounter data.

Bioinformatics btz647 (2019). doi:10.1093/bioinformatics/btz647

24.

Cosentino, C., Cnop, M. & Igoillo-Esteve, M.

The tRNA Epitranscriptome and Diabetes: Emergence of tRNA Hypomodifications as a Cause of Pancreatic β-Cell Failure.

Endocrinology 160, 1262–1274 (2019). doi:10.1210/en.2019-00098

25.

Lytrivi, M., Igoillo-Esteve, M. & Cnop, M.

Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.

Current Opinion in Pharmacology 43, 40–45 (2018). doi:10.1016/j.coph.2018.08.002

Dragan, I., Sparso, T., Kuznetsov, D., Slieker, R. & Ibberson, M.

dsSwissKnife: An R package for federated data analysis.

bioRxiv 2020.11.17.386813 (2020). doi:10.1101/2020.11.17.386813

Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.

The Journal of Clinical Endocrinology & Metabolism 105, dgaa435 (2020). doi:10.1210/clinem/dgaa435

Hu, M., Cherkaoui, I., Misra, S. & Rutter, G. A.

Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.

Frontiers in Endocrinology 11, 576632 (2020). doi:10.3389/fendo.2020.576632

Muniangi-Muhitu, H., Akalestou, E., Salem, V., Misra, S., Oliver, N. S. & Rutter, G. A.

Covid-19 and Diabetes: A Complex Bidirectional Relationship.

Frontiers in Endocrinology 11, 582936 (2020). doi:10.3389/fendo.2020.582936

Jennings, R. E., Scharfmann, R. & Staels, W.

Transcription factors that shape the mammalian pancreas.

Diabetologia 63, 1974–1980 (2020). doi:10.1007/s00125-020-05161-0

Leal, J., Reed, S. D., Patel, R., Rivero-Arias, O., Li, Y., Schulman, K. A., Califf, R. M., Holman, R. R. & Gray, A. M.

Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data.

Diabetes Care 43, 2485–2492 (2020). doi:10.2337/dc20-0717

Vasiljević, J., Torkko, J. M., Knoch, K.-P. & Solimena, M.

The making of insulin in health and disease.

Diabetologia 63, 1981–1989 (2020). doi:10.1007/s00125-020-05192-7

Evaluating the Ability of Economic Models of Diabetes to Simulate New Cardiovascular Outcomes Trials: A Report on the Ninth Mount Hood Diabetes Challenge.

Value in Health 23, 1163–1170 (2020). doi:10.1016/j.jval.2020.04.1832

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice.

EBioMedicine 58, 102895 (2020). doi:10.1016/j.ebiom.2020.102895

10.

The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse.

Biomolecules 10, 1057 (2020). doi:10.3390/biom10071057

11.

Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis.

bioRxiv 2020.05.18.099200 (2020). doi:10.1101/2020.05.18.099200

12.

Akalestou, E., Suba, K., Lopez-Noriega, L., Georgiadou, E., Chabosseau, P., Leclerc, I., Salem, V. & Rutter, G. A.

Intravital imaging of islet Ca 2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.05.05.078725.

13.

Clough, T. J., Baxan, N., Coakley, E. J., Rivas, C., Zhao, L., Leclerc, I., Martinez-Sanchez, A., Rutter, G. A. & Long, N. J.

Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.

Dalton Transactions 49, 4732–4740 (2020). doi:10.1039/D0DT00332H

14.

Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a new regulator of insulin secretion.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.31.017707.

15.

Bouland, G. A., Beulens, J. W., Nap, J., van der Slik, A. R., Zaldumbide, A., Hart, L. M. & Slieker, R. C.

Understanding functional consequences of type 2 diabetes risk loci using the universal data integration and visualization R package CONQUER.

(Genomics, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.27.011627.

16.

The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.

bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286

17.

Fang, Z., Chen, S., Pickford, P., Broichhagen, J., Hodson, D. J., Corrêa, I. R., Kumar, S., Görlitz, F., Dunsby, C., French, P., Rutter, G. A., Tan, T., Bloom, S. R., Tomas, A. & Jones, B.

The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.

bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524

18.

Dumayne, C., Tarussio, D., Sanchez-Archidona, A. R., Picard, A., Basco, D., Berney, X. P., Ibberson, M. & Thorens, B.

Klf6 protects β-cells against insulin resistance-induced dedifferentiation.

Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001

19.

The pore-forming subunit MCU of the mitochondrial Ca2+ uniporter is required for normal glucose-stimulated insulin secretion in vitro and in vivo in mice.

Diabetologia 63, 1368–1381 (2020). doi:10.1007/s00125-020-05148-x

20.

Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.

Diabetologia 63, 395–409 (2020). doi:10.1007/s00125-019-05046-x

21.

Scharfmann, R., Staels, W. & Albagli, O.

The supply chain of human pancreatic β cell lines.

The Journal of Clinical Investigation 129, 3511–3520 (2019). doi:10.1172/JCI129484

22.

Barovic, M., Distler, M., Schöniger, E., Radisch, N., Aust, D., Weitz, J., Ibberson, M., Schulte, A. M. & Solimena, M.

Metabolically phenotyped pancreatectomized patients as living donors for the study of islets in health and diabetes.

Molecular Metabolism 27, S1-S6 (2019). doi:10.1016/j.molmet.2019.06.006

23.

Canouil, M., Bouland, G. A., Bonnefond, A., Froguel, P., ’t Hart, L. M. & Slieker, R. C.

NACHO: an R package for quality control of NanoString nCounter data.

Bioinformatics btz647 (2019). doi:10.1093/bioinformatics/btz647

24.

Cosentino, C., Cnop, M. & Igoillo-Esteve, M.

The tRNA Epitranscriptome and Diabetes: Emergence of tRNA Hypomodifications as a Cause of Pancreatic β-Cell Failure.

Endocrinology 160, 1262–1274 (2019). doi:10.1210/en.2019-00098

25.

Lytrivi, M., Igoillo-Esteve, M. & Cnop, M.

Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.

Current Opinion in Pharmacology 43, 40–45 (2018). doi:10.1016/j.coph.2018.08.002

Dragan, I., Sparso, T., Kuznetsov, D., Slieker, R. & Ibberson, M.

dsSwissKnife: An R package for federated data analysis.

bioRxiv 2020.11.17.386813 (2020). doi:10.1101/2020.11.17.386813

Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.

The Journal of Clinical Endocrinology & Metabolism 105, dgaa435 (2020). doi:10.1210/clinem/dgaa435

Hu, M., Cherkaoui, I., Misra, S. & Rutter, G. A.

Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.

Frontiers in Endocrinology 11, 576632 (2020). doi:10.3389/fendo.2020.576632

Muniangi-Muhitu, H., Akalestou, E., Salem, V., Misra, S., Oliver, N. S. & Rutter, G. A.

Covid-19 and Diabetes: A Complex Bidirectional Relationship.

Frontiers in Endocrinology 11, 582936 (2020). doi:10.3389/fendo.2020.582936

Jennings, R. E., Scharfmann, R. & Staels, W.

Transcription factors that shape the mammalian pancreas.

Diabetologia 63, 1974–1980 (2020). doi:10.1007/s00125-020-05161-0

Leal, J., Reed, S. D., Patel, R., Rivero-Arias, O., Li, Y., Schulman, K. A., Califf, R. M., Holman, R. R. & Gray, A. M.

Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data.

Diabetes Care 43, 2485–2492 (2020). doi:10.2337/dc20-0717

Vasiljević, J., Torkko, J. M., Knoch, K.-P. & Solimena, M.

The making of insulin in health and disease.

Diabetologia 63, 1981–1989 (2020). doi:10.1007/s00125-020-05192-7

Evaluating the Ability of Economic Models of Diabetes to Simulate New Cardiovascular Outcomes Trials: A Report on the Ninth Mount Hood Diabetes Challenge.

Value in Health 23, 1163–1170 (2020). doi:10.1016/j.jval.2020.04.1832

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice.

EBioMedicine 58, 102895 (2020). doi:10.1016/j.ebiom.2020.102895

10.

The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse.

Biomolecules 10, 1057 (2020). doi:10.3390/biom10071057

11.

Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis.

bioRxiv 2020.05.18.099200 (2020). doi:10.1101/2020.05.18.099200

12.

Akalestou, E., Suba, K., Lopez-Noriega, L., Georgiadou, E., Chabosseau, P., Leclerc, I., Salem, V. & Rutter, G. A.

Intravital imaging of islet Ca 2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.05.05.078725.

13.

Clough, T. J., Baxan, N., Coakley, E. J., Rivas, C., Zhao, L., Leclerc, I., Martinez-Sanchez, A., Rutter, G. A. & Long, N. J.

Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.

Dalton Transactions 49, 4732–4740 (2020). doi:10.1039/D0DT00332H

14.

Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a new regulator of insulin secretion.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.31.017707.

15.

Bouland, G. A., Beulens, J. W., Nap, J., van der Slik, A. R., Zaldumbide, A., Hart, L. M. & Slieker, R. C.

Understanding functional consequences of type 2 diabetes risk loci using the universal data integration and visualization R package CONQUER.

(Genomics, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.27.011627.

16.

The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.

bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286

17.

Fang, Z., Chen, S., Pickford, P., Broichhagen, J., Hodson, D. J., Corrêa, I. R., Kumar, S., Görlitz, F., Dunsby, C., French, P., Rutter, G. A., Tan, T., Bloom, S. R., Tomas, A. & Jones, B.

The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.

bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524

18.

Dumayne, C., Tarussio, D., Sanchez-Archidona, A. R., Picard, A., Basco, D., Berney, X. P., Ibberson, M. & Thorens, B.

Klf6 protects β-cells against insulin resistance-induced dedifferentiation.

Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001

19.

The pore-forming subunit MCU of the mitochondrial Ca2+ uniporter is required for normal glucose-stimulated insulin secretion in vitro and in vivo in mice.

Diabetologia 63, 1368–1381 (2020). doi:10.1007/s00125-020-05148-x

20.

Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.

Diabetologia 63, 395–409 (2020). doi:10.1007/s00125-019-05046-x

21.

Scharfmann, R., Staels, W. & Albagli, O.

The supply chain of human pancreatic β cell lines.

The Journal of Clinical Investigation 129, 3511–3520 (2019). doi:10.1172/JCI129484

22.

Barovic, M., Distler, M., Schöniger, E., Radisch, N., Aust, D., Weitz, J., Ibberson, M., Schulte, A. M. & Solimena, M.

Metabolically phenotyped pancreatectomized patients as living donors for the study of islets in health and diabetes.

Molecular Metabolism 27, S1-S6 (2019). doi:10.1016/j.molmet.2019.06.006

23.

Canouil, M., Bouland, G. A., Bonnefond, A., Froguel, P., ’t Hart, L. M. & Slieker, R. C.

NACHO: an R package for quality control of NanoString nCounter data.

Bioinformatics btz647 (2019). doi:10.1093/bioinformatics/btz647

24.

Cosentino, C., Cnop, M. & Igoillo-Esteve, M.

The tRNA Epitranscriptome and Diabetes: Emergence of tRNA Hypomodifications as a Cause of Pancreatic β-Cell Failure.

Endocrinology 160, 1262–1274 (2019). doi:10.1210/en.2019-00098

25.

Lytrivi, M., Igoillo-Esteve, M. & Cnop, M.

Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.

Current Opinion in Pharmacology 43, 40–45 (2018). doi:10.1016/j.coph.2018.08.002

Dragan, I., Sparso, T., Kuznetsov, D., Slieker, R. & Ibberson, M.

dsSwissKnife: An R package for federated data analysis.

bioRxiv 2020.11.17.386813 (2020). doi:10.1101/2020.11.17.386813

Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.

The Journal of Clinical Endocrinology & Metabolism 105, dgaa435 (2020). doi:10.1210/clinem/dgaa435

Hu, M., Cherkaoui, I., Misra, S. & Rutter, G. A.

Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.

Frontiers in Endocrinology 11, 576632 (2020). doi:10.3389/fendo.2020.576632

Muniangi-Muhitu, H., Akalestou, E., Salem, V., Misra, S., Oliver, N. S. & Rutter, G. A.

Covid-19 and Diabetes: A Complex Bidirectional Relationship.

Frontiers in Endocrinology 11, 582936 (2020). doi:10.3389/fendo.2020.582936

Jennings, R. E., Scharfmann, R. & Staels, W.

Transcription factors that shape the mammalian pancreas.

Diabetologia 63, 1974–1980 (2020). doi:10.1007/s00125-020-05161-0

Leal, J., Reed, S. D., Patel, R., Rivero-Arias, O., Li, Y., Schulman, K. A., Califf, R. M., Holman, R. R. & Gray, A. M.

Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data.

Diabetes Care 43, 2485–2492 (2020). doi:10.2337/dc20-0717

Vasiljević, J., Torkko, J. M., Knoch, K.-P. & Solimena, M.

The making of insulin in health and disease.

Diabetologia 63, 1981–1989 (2020). doi:10.1007/s00125-020-05192-7

Evaluating the Ability of Economic Models of Diabetes to Simulate New Cardiovascular Outcomes Trials: A Report on the Ninth Mount Hood Diabetes Challenge.

Value in Health 23, 1163–1170 (2020). doi:10.1016/j.jval.2020.04.1832

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice.

EBioMedicine 58, 102895 (2020). doi:10.1016/j.ebiom.2020.102895

10.

The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse.

Biomolecules 10, 1057 (2020). doi:10.3390/biom10071057

11.

Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis.

bioRxiv 2020.05.18.099200 (2020). doi:10.1101/2020.05.18.099200

12.

Akalestou, E., Suba, K., Lopez-Noriega, L., Georgiadou, E., Chabosseau, P., Leclerc, I., Salem, V. & Rutter, G. A.

Intravital imaging of islet Ca 2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.05.05.078725.

13.

Clough, T. J., Baxan, N., Coakley, E. J., Rivas, C., Zhao, L., Leclerc, I., Martinez-Sanchez, A., Rutter, G. A. & Long, N. J.

Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.

Dalton Transactions 49, 4732–4740 (2020). doi:10.1039/D0DT00332H

14.

Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a new regulator of insulin secretion.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.31.017707.

15.

Bouland, G. A., Beulens, J. W., Nap, J., van der Slik, A. R., Zaldumbide, A., Hart, L. M. & Slieker, R. C.

Understanding functional consequences of type 2 diabetes risk loci using the universal data integration and visualization R package CONQUER.

(Genomics, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.27.011627.

16.

The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.

bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286

17.

Fang, Z., Chen, S., Pickford, P., Broichhagen, J., Hodson, D. J., Corrêa, I. R., Kumar, S., Görlitz, F., Dunsby, C., French, P., Rutter, G. A., Tan, T., Bloom, S. R., Tomas, A. & Jones, B.

The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.

bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524

18.

Dumayne, C., Tarussio, D., Sanchez-Archidona, A. R., Picard, A., Basco, D., Berney, X. P., Ibberson, M. & Thorens, B.

Klf6 protects β-cells against insulin resistance-induced dedifferentiation.

Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001

19.

The pore-forming subunit MCU of the mitochondrial Ca2+ uniporter is required for normal glucose-stimulated insulin secretion in vitro and in vivo in mice.

Diabetologia 63, 1368–1381 (2020). doi:10.1007/s00125-020-05148-x

20.

Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.

Diabetologia 63, 395–409 (2020). doi:10.1007/s00125-019-05046-x

21.

Scharfmann, R., Staels, W. & Albagli, O.

The supply chain of human pancreatic β cell lines.

The Journal of Clinical Investigation 129, 3511–3520 (2019). doi:10.1172/JCI129484

22.

Barovic, M., Distler, M., Schöniger, E., Radisch, N., Aust, D., Weitz, J., Ibberson, M., Schulte, A. M. & Solimena, M.

Metabolically phenotyped pancreatectomized patients as living donors for the study of islets in health and diabetes.

Molecular Metabolism 27, S1-S6 (2019). doi:10.1016/j.molmet.2019.06.006

23.

Canouil, M., Bouland, G. A., Bonnefond, A., Froguel, P., ’t Hart, L. M. & Slieker, R. C.

NACHO: an R package for quality control of NanoString nCounter data.

Bioinformatics btz647 (2019). doi:10.1093/bioinformatics/btz647

24.

Cosentino, C., Cnop, M. & Igoillo-Esteve, M.

The tRNA Epitranscriptome and Diabetes: Emergence of tRNA Hypomodifications as a Cause of Pancreatic β-Cell Failure.

Endocrinology 160, 1262–1274 (2019). doi:10.1210/en.2019-00098

25.

Lytrivi, M., Igoillo-Esteve, M. & Cnop, M.

Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.

Current Opinion in Pharmacology 43, 40–45 (2018). doi:10.1016/j.coph.2018.08.002

Dragan, I., Sparso, T., Kuznetsov, D., Slieker, R. & Ibberson, M.

dsSwissKnife: An R package for federated data analysis.

bioRxiv 2020.11.17.386813 (2020). doi:10.1101/2020.11.17.386813

Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.

The Journal of Clinical Endocrinology & Metabolism 105, dgaa435 (2020). doi:10.1210/clinem/dgaa435

Hu, M., Cherkaoui, I., Misra, S. & Rutter, G. A.

Functional Genomics in Pancreatic β Cells: Recent Advances in Gene Deletion and Genome Editing Technologies for Diabetes Research.

Frontiers in Endocrinology 11, 576632 (2020). doi:10.3389/fendo.2020.576632

Muniangi-Muhitu, H., Akalestou, E., Salem, V., Misra, S., Oliver, N. S. & Rutter, G. A.

Covid-19 and Diabetes: A Complex Bidirectional Relationship.

Frontiers in Endocrinology 11, 582936 (2020). doi:10.3389/fendo.2020.582936

Jennings, R. E., Scharfmann, R. & Staels, W.

Transcription factors that shape the mammalian pancreas.

Diabetologia 63, 1974–1980 (2020). doi:10.1007/s00125-020-05161-0

Leal, J., Reed, S. D., Patel, R., Rivero-Arias, O., Li, Y., Schulman, K. A., Califf, R. M., Holman, R. R. & Gray, A. M.

Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data.

Diabetes Care 43, 2485–2492 (2020). doi:10.2337/dc20-0717

Vasiljević, J., Torkko, J. M., Knoch, K.-P. & Solimena, M.

The making of insulin in health and disease.

Diabetologia 63, 1981–1989 (2020). doi:10.1007/s00125-020-05192-7

Evaluating the Ability of Economic Models of Diabetes to Simulate New Cardiovascular Outcomes Trials: A Report on the Ninth Mount Hood Diabetes Challenge.

Value in Health 23, 1163–1170 (2020). doi:10.1016/j.jval.2020.04.1832

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice.

EBioMedicine 58, 102895 (2020). doi:10.1016/j.ebiom.2020.102895

10.

The Constitutive Lack of α7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse.

Biomolecules 10, 1057 (2020). doi:10.3390/biom10071057

11.

Sexually dimorphic roles for the type 2 diabetes-associated C2cd4b gene in murine glucose homeostasis.

bioRxiv 2020.05.18.099200 (2020). doi:10.1101/2020.05.18.099200

12.

Akalestou, E., Suba, K., Lopez-Noriega, L., Georgiadou, E., Chabosseau, P., Leclerc, I., Salem, V. & Rutter, G. A.

Intravital imaging of islet Ca 2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.05.05.078725.

13.

Clough, T. J., Baxan, N., Coakley, E. J., Rivas, C., Zhao, L., Leclerc, I., Martinez-Sanchez, A., Rutter, G. A. & Long, N. J.

Synthesis and in vivo behaviour of an exendin-4-based MRI probe capable of β-cell-dependent contrast enhancement in the pancreas.

Dalton Transactions 49, 4732–4740 (2020). doi:10.1039/D0DT00332H

14.

Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a new regulator of insulin secretion.

(Cell Biology, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.31.017707.

15.

Bouland, G. A., Beulens, J. W., Nap, J., van der Slik, A. R., Zaldumbide, A., Hart, L. M. & Slieker, R. C.

Understanding functional consequences of type 2 diabetes risk loci using the universal data integration and visualization R package CONQUER.

(Genomics, 2020). http://biorxiv.org/lookup/doi/10.1101/2020.03.27.011627.

16.

The type 2 diabetes gene product STARD10 is a phosphoinositide binding protein that controls insulin secretory granule biogenesis.

bioRxiv 2020.03.25.007286 (2020). doi:10.1101/2020.03.25.007286

17.

Fang, Z., Chen, S., Pickford, P., Broichhagen, J., Hodson, D. J., Corrêa, I. R., Kumar, S., Görlitz, F., Dunsby, C., French, P., Rutter, G. A., Tan, T., Bloom, S. R., Tomas, A. & Jones, B.

The influence of peptide context on signalling and trafficking of glucagon-like peptide-1 receptor biased agonists.

bioRxiv 2020.02.24.961524 (2020). doi:10.1101/2020.02.24.961524

18.

Dumayne, C., Tarussio, D., Sanchez-Archidona, A. R., Picard, A., Basco, D., Berney, X. P., Ibberson, M. & Thorens, B.

Klf6 protects β-cells against insulin resistance-induced dedifferentiation.

Molecular Metabolism (2020). doi:10.1016/j.molmet.2020.02.001

19.

The pore-forming subunit MCU of the mitochondrial Ca2+ uniporter is required for normal glucose-stimulated insulin secretion in vitro and in vivo in mice.

Diabetologia 63, 1368–1381 (2020). doi:10.1007/s00125-020-05148-x

20.

Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity.

Diabetologia 63, 395–409 (2020). doi:10.1007/s00125-019-05046-x

21.

Scharfmann, R., Staels, W. & Albagli, O.

The supply chain of human pancreatic β cell lines.

The Journal of Clinical Investigation 129, 3511–3520 (2019). doi:10.1172/JCI129484

22.

Barovic, M., Distler, M., Schöniger, E., Radisch, N., Aust, D., Weitz, J., Ibberson, M., Schulte, A. M. & Solimena, M.

Metabolically phenotyped pancreatectomized patients as living donors for the study of islets in health and diabetes.

Molecular Metabolism 27, S1-S6 (2019). doi:10.1016/j.molmet.2019.06.006

23.

Canouil, M., Bouland, G. A., Bonnefond, A., Froguel, P., ’t Hart, L. M. & Slieker, R. C.

NACHO: an R package for quality control of NanoString nCounter data.

Bioinformatics btz647 (2019). doi:10.1093/bioinformatics/btz647

24.

Cosentino, C., Cnop, M. & Igoillo-Esteve, M.

The tRNA Epitranscriptome and Diabetes: Emergence of tRNA Hypomodifications as a Cause of Pancreatic β-Cell Failure.

Endocrinology 160, 1262–1274 (2019). doi:10.1210/en.2019-00098

25.

Lytrivi, M., Igoillo-Esteve, M. & Cnop, M.

Inflammatory stress in islet β-cells: therapeutic implications for type 2 diabetes?.

Current Opinion in Pharmacology 43, 40–45 (2018). doi:10.1016/j.coph.2018.08.002

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This project receives funding from the Innovative Medicines Initiative 2 Joint Undertaking (www.imi.europa.eu) under grant agreement No 115881. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.

This work is supported by the Swiss State Secretariat for Education‚ Research and Innovation (SERI) under contract number 16.0097-2.

The opinions expressed and arguments employed herein do not necessarily reflect the official views of these funding bodies.