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

Mutie, P. M., Pomares-Millan, H., Atabaki-Pasdar, N., Jordan, N., Adams, R., Daly, N. L., Tajes, J. F., Giordano, G. N. & Franks, P. W.

An investigation of causal relationships between prediabetes and vascular complications.

Nature Communications 11, 4592 (2020). doi:10.1038/s41467-020-18386-9

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

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

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

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

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.

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

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

Dominguez-Meijide, A., Vasili, E., König, A., Cima-Omori, M.-S., Leonov, A., Ryazanov, S., Zweckstetter, M., Griesinger, C. & Outeiro, T. F.

Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.

bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643

10.

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

11.

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

12.

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

13.

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

14.

Thorens, B., Rodriguez, A., Cruciani-Guglielmacci, C., Wigger, L., Ibberson, M. & Magnan, C.

Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.

Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008

15.

Marchetti, P., Schulte, A. M., Marselli, L., Schoniger, E., Bugliani, M., Kramer, W., Overbergh, L., Ullrich, S., Gloyn, A. L., Ibberson, M., Rutter, G., Froguel, P., Groop, L., McCarthy, M. I., Dotta, F., Scharfmann, R., Magnan, C., Eizirik, D. L., Mathieu, C., Cnop, M., Thorens, B. & Solimena, M.

Fostering improved human islet research: a European perspective.

Diabetologia 62, 1514–1516 (2019). doi:10.1007/s00125-019-4911-4

16.

Salem, V., Silva, L. D., Suba, K., Georgiadou, E., Gharavy, S. N. M., Akhtar, N., Martin-Alonso, A., Gaboriau, D. C. A., Rothery, S. M., Stylianides, T., Carrat, G., Pullen, T. J., Singh, S. P., Hodson, D. J., Leclerc, I., Shapiro, A. M. J., Marchetti, P., Briant, L. J. B., Distaso, W., Ninov, N. & Rutter, G. A.

Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.

Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2

17.

Khamis, A., Canouil, M., Siddiq, A., Crouch, H., Falchi, M., Bulow, M. von, Ehehalt, F., Marselli, L., Distler, M., Richter, D., Weitz, J., Bokvist, K., Xenarios, I., Thorens, B., Schulte, A. M., Ibberson, M., Bonnefond, A., Marchetti, P., Solimena, M. & Froguel, P.

Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.

Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004

18.

Toledo, P. L., Torkko, J. M., Müller, A., Wegbrod, C., Sönmez, A., Solimena, M. & Ermácora, M. R.

ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.

bioRxiv 521351 (2019). doi:10.1101/521351

19.

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

20.

Cosentino, C., Toivonen, S., Diaz Villamil, E., Atta, M., Ravanat, J.-L., Demine, S., Schiavo, A., Pachera, N., Deglasse, J.-P., Jonas, J.-C., Balboa, D., Otonkoski, T., Pearson, E. R., Marchetti, P., Eizirik, D. L., Cnop, M. & Igoillo-Esteve, M.

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302–10318 (2018). doi:10.1093/nar/gky839

21.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet.

Diabetes, Obesity and Metabolism 19, 30–41 (2017). doi:10.1111/dom.12990

22.

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 doi:10.1093/bioinformatics/btz647

23.

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 doi:10.1210/en.2019-00098

24.

Leal, J., Morrow, L. M., Khurshid, W., Pagano, E. & Feenstra, T.

Decision models of prediabetes populations: A systematic review.

Diabetes, Obesity and Metabolism doi:10.1111/dom.13684

25.

Wagner, R., Jaghutriz, B. A., Gerst, F., Barroso Oquendo, M., Machann, J., Schick, F., Löffler, M., 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 doi:10.1210/clinem/dgaa435

Mutie, P. M., Pomares-Millan, H., Atabaki-Pasdar, N., Jordan, N., Adams, R., Daly, N. L., Tajes, J. F., Giordano, G. N. & Franks, P. W.

An investigation of causal relationships between prediabetes and vascular complications.

Nature Communications 11, 4592 (2020). doi:10.1038/s41467-020-18386-9

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

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

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

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

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

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.

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

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

Dominguez-Meijide, A., Vasili, E., König, A., Cima-Omori, M.-S., Leonov, A., Ryazanov, S., Zweckstetter, M., Griesinger, C. & Outeiro, T. F.

Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.

bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643

10.

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

11.

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

12.

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

13.

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

14.

Thorens, B., Rodriguez, A., Cruciani-Guglielmacci, C., Wigger, L., Ibberson, M. & Magnan, C.

Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.

Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008

15.

Fostering improved human islet research: a European perspective.

Diabetologia 62, 1514–1516 (2019). doi:10.1007/s00125-019-4911-4

16.

Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.

Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2

17.

Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.

Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004

18.

Toledo, P. L., Torkko, J. M., Müller, A., Wegbrod, C., Sönmez, A., Solimena, M. & Ermácora, M. R.

ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.

bioRxiv 521351 (2019). doi:10.1101/521351

19.

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

20.

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302–10318 (2018). doi:10.1093/nar/gky839

21.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet.

Diabetes, Obesity and Metabolism 19, 30–41 (2017). doi:10.1111/dom.12990

22.

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 doi:10.1093/bioinformatics/btz647

23.

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 doi:10.1210/en.2019-00098

24.

Leal, J., Morrow, L. M., Khurshid, W., Pagano, E. & Feenstra, T.

Decision models of prediabetes populations: A systematic review.

Diabetes, Obesity and Metabolism doi:10.1111/dom.13684

25.

Pancreatic steatosis associates with impaired insulin secretion in genetically predisposed individuals.

The Journal of Clinical Endocrinology & Metabolism doi:10.1210/clinem/dgaa435

Mutie, P. M., Pomares-Millan, H., Atabaki-Pasdar, N., Jordan, N., Adams, R., Daly, N. L., Tajes, J. F., Giordano, G. N. & Franks, P. W.

An investigation of causal relationships between prediabetes and vascular complications.

Nature Communications 11, 4592 (2020). doi:10.1038/s41467-020-18386-9

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

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

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

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

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

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.

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

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

Dominguez-Meijide, A., Vasili, E., König, A., Cima-Omori, M.-S., Leonov, A., Ryazanov, S., Zweckstetter, M., Griesinger, C. & Outeiro, T. F.

Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.

bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643

10.

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

11.

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

12.

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

13.

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

14.

Thorens, B., Rodriguez, A., Cruciani-Guglielmacci, C., Wigger, L., Ibberson, M. & Magnan, C.

Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.

Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008

15.

Fostering improved human islet research: a European perspective.

Diabetologia 62, 1514–1516 (2019). doi:10.1007/s00125-019-4911-4

16.

Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.

Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2

17.

Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.

Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004

18.

Toledo, P. L., Torkko, J. M., Müller, A., Wegbrod, C., Sönmez, A., Solimena, M. & Ermácora, M. R.

ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.

bioRxiv 521351 (2019). doi:10.1101/521351

19.

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

20.

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302–10318 (2018). doi:10.1093/nar/gky839

21.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet.

Diabetes, Obesity and Metabolism 19, 30–41 (2017). doi:10.1111/dom.12990

22.

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 doi:10.1093/bioinformatics/btz647

23.

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 doi:10.1210/en.2019-00098

24.

Leal, J., Morrow, L. M., Khurshid, W., Pagano, E. & Feenstra, T.

Decision models of prediabetes populations: A systematic review.

Diabetes, Obesity and Metabolism doi:10.1111/dom.13684

25.

Pancreatic steatosis associates with impaired insulin secretion in genetically predisposed individuals.

The Journal of Clinical Endocrinology & Metabolism doi:10.1210/clinem/dgaa435

Mutie, P. M., Pomares-Millan, H., Atabaki-Pasdar, N., Jordan, N., Adams, R., Daly, N. L., Tajes, J. F., Giordano, G. N. & Franks, P. W.

An investigation of causal relationships between prediabetes and vascular complications.

Nature Communications 11, 4592 (2020). doi:10.1038/s41467-020-18386-9

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

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

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

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

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

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.

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

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

Dominguez-Meijide, A., Vasili, E., König, A., Cima-Omori, M.-S., Leonov, A., Ryazanov, S., Zweckstetter, M., Griesinger, C. & Outeiro, T. F.

Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.

bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643

10.

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

11.

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

12.

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

13.

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

14.

Thorens, B., Rodriguez, A., Cruciani-Guglielmacci, C., Wigger, L., Ibberson, M. & Magnan, C.

Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.

Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008

15.

Fostering improved human islet research: a European perspective.

Diabetologia 62, 1514–1516 (2019). doi:10.1007/s00125-019-4911-4

16.

Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.

Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2

17.

Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.

Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004

18.

Toledo, P. L., Torkko, J. M., Müller, A., Wegbrod, C., Sönmez, A., Solimena, M. & Ermácora, M. R.

ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.

bioRxiv 521351 (2019). doi:10.1101/521351

19.

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

20.

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302–10318 (2018). doi:10.1093/nar/gky839

21.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet.

Diabetes, Obesity and Metabolism 19, 30–41 (2017). doi:10.1111/dom.12990

22.

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 doi:10.1093/bioinformatics/btz647

23.

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 doi:10.1210/en.2019-00098

24.

Leal, J., Morrow, L. M., Khurshid, W., Pagano, E. & Feenstra, T.

Decision models of prediabetes populations: A systematic review.

Diabetes, Obesity and Metabolism doi:10.1111/dom.13684

25.

Pancreatic steatosis associates with impaired insulin secretion in genetically predisposed individuals.

The Journal of Clinical Endocrinology & Metabolism doi:10.1210/clinem/dgaa435

Mutie, P. M., Pomares-Millan, H., Atabaki-Pasdar, N., Jordan, N., Adams, R., Daly, N. L., Tajes, J. F., Giordano, G. N. & Franks, P. W.

An investigation of causal relationships between prediabetes and vascular complications.

Nature Communications 11, 4592 (2020). doi:10.1038/s41467-020-18386-9

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

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

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

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

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

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.

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

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

Dominguez-Meijide, A., Vasili, E., König, A., Cima-Omori, M.-S., Leonov, A., Ryazanov, S., Zweckstetter, M., Griesinger, C. & Outeiro, T. F.

Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.

bioRxiv 2020.01.27.921643 (2020). doi:10.1101/2020.01.27.921643

10.

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

11.

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

12.

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

13.

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

14.

Thorens, B., Rodriguez, A., Cruciani-Guglielmacci, C., Wigger, L., Ibberson, M. & Magnan, C.

Use of preclinical models to identify markers of type 2 diabetes susceptibility and novel regulators of insulin secretion – A step towards precision medicine.

Molecular Metabolism 27, S147-S154 (2019). doi:10.1016/j.molmet.2019.06.008

15.

Fostering improved human islet research: a European perspective.

Diabetologia 62, 1514–1516 (2019). doi:10.1007/s00125-019-4911-4

16.

Leader β-cells coordinate Ca 2+ dynamics across pancreatic islets in vivo.

Nature Metabolism 1, 615 (2019). doi:10.1038/s42255-019-0075-2

17.

Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.

Molecular Metabolism (2019). doi:10.1016/j.molmet.2019.03.004

18.

Toledo, P. L., Torkko, J. M., Müller, A., Wegbrod, C., Sönmez, A., Solimena, M. & Ermácora, M. R.

ICA512 RESP18 homology domain is a protein condensing factor and insulin fibrillation inhibitor.

bioRxiv 521351 (2019). doi:10.1101/521351

19.

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

20.

Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes.

Nucleic Acids Research 46, 10302–10318 (2018). doi:10.1093/nar/gky839

21.

Rutter, G. A., Hodson, D. J., Chabosseau, P., Haythorne, E., Pullen, T. J. & Leclerc, I.

Local and regional control of calcium dynamics in the pancreatic islet.

Diabetes, Obesity and Metabolism 19, 30–41 (2017). doi:10.1111/dom.12990

22.

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 doi:10.1093/bioinformatics/btz647

23.

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 doi:10.1210/en.2019-00098

24.

Leal, J., Morrow, L. M., Khurshid, W., Pagano, E. & Feenstra, T.

Decision models of prediabetes populations: A systematic review.

Diabetes, Obesity and Metabolism doi:10.1111/dom.13684

25.

Pancreatic steatosis associates with impaired insulin secretion in genetically predisposed individuals.

The Journal of Clinical Endocrinology & Metabolism doi:10.1210/clinem/dgaa435

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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.