Translational research on diabetes (RTD)

 

Lille University – Lille University Hospital – Inserm U1190 – Institut Pasteur de Lille
Director : François Pattou

The Laboratory for Translational Research on Diabetes is a joint research unit of the University of Lille, Inserm, Lille University Hospital and the Pasteur Institute of Lille. Initially labelled by INSERM as ERIT-M in 2000, our team became UNIT-M in 2005, then U859 in 2009 and UMR – 1190 in 2015. In 2009, we joined Philippe Froguel and Bart Staels’ team to form the Research Federation of the European Genomic Institute for Diabetes (EGID) which was awarded in 2011 as a Laboratory of Excellence (Labex) by the Programme d’Investissements d’Avenir [PIA].

The research team is located on the campus of Lille University Hospital, in the Research Pole of the Faculty of Medicine and includes a Biotherapy Platform for the production of human islets, an Animal Facility (rodents and mini-pigs) and the DiabInnov platform (industry-university platform). All the clinical studies are conducted at the Huriez Hospital, adjacent to our laboratory.

Recherche translationnelle sur le diabète

Presentation

The unit focuses on translational research on diabetes and in particular on human islet transplantation and metabolic surgery. The overall mission of our unit is the development of innovative therapies for severe forms of diabetes and their clinical application. Our scientific objectives are focused on the production of human islets and the treatment of type 1 diabetes through islet transplantation, and the treatment of type 2 diabetes through metabolic surgery. A key feature of our research strategy is the bringing together of clinical researchers, endocrine surgeons and diabetologists, under the aegis of a single team, with a veterinarian and biologists, who join forces to take research from the laboratory to the bedside. This original typology has appeared particularly suited to translational research on diabetes, and has enabled strategies previously developed in the laboratory and validated in the animal model to be successfully and repeatedly transposed into clinics. In addition, our clinical studies often involve invasive techniques, which offer many opportunities to access, in strict compliance with regulatory requirements, valuable human biological samples, such as pancreatic islets or other metabolic tissues. Thus, we have developed experimental and mechanistic studies based on human islets and our animal models.

Highlights

  • We discovered the specific expression on the sodium-glucose-co-transporters 1 (SGLT1) and SGLT2 in human pancreatic alpha cells, where SGLT2 inhibition triggered glucagon secretion (Bonner et al., Nature Medicine 2015).

  • We identified sodium as a key factor in intestinal glucose absorption, and showed that Roux-en-Y gastric bypass decreased sodium normally brought into the intestine with bile, thereby impairing intestinal glucose uptake via sodium-glucose cotransport (Baud et al., Cell Metabolism 2016).

  • We demonstrated that non islet cells (ductal cells and exocrine tissue) have a beneficial effect on long-term islet graft function, possible through ductal-to-endocrine cell differentiation (Benolmar K at al. AMJT, 2018)

  • We demonstrated, for the first time thar human islet transplantation corrects type 1 diabetes for a duration of 10 years (Vantyghem MC et al. Diabetes Care, 2019)

  • Using five complementary models (db/db mice, healthy C57BL/6J mice, human islet cultures, diet-induced obese mice, and SSTR2 KO mice), we further demonstrated that the combination of the GLP1R agonist liraglutide and the SGLT2 inhibitor dapagliflozin improved glycemia and reduced dapagliflozin induced glucagon secretion via somatostatin release (Saponaro et al., Cell Reports, 2019).

  • Using an unbiased RNA-sequencing analysis of 207 pancreatic donors and confocal immunofluorescent imaging analysis on 665 islets from 12 pancreatic donors revealed an unprecedented level of heterogeneity of SLC5A2 gene and SGLT2 protein expression in human alpha cells Saponaro et al., Diabetes, 2020).

  • Using Western blotting technique, as an important tool for researchers, we demonstrated that proglucagon-derived peptides expression and regulation can be verified in primary islets in response to various metabolic stimuli (Acosta-Montalvo et al., Frontiers in Cell and Developmental Biology, 2020).

Members

François PATTOU
Director of laboratory, professor of medicine
ORCID number : 0000-0001-8388-3766

Julie KERR-CONTE
Professor
Numéro ORCID : 0000-0002-7590-1896

Marie-Christine VANTYGHEM
Professor

Valéry GMYR
Research engineer
ORCID number : 0000-0003-1236-359X

Thomas HUBERT
MCU

Caroline BONNER
Researcher, group leader
ORCID number : 0000-0002-4430-8280

Violeta RAVERDY
Doctor of medicine

Chiara SAPONARO
Post-doc

Mikael CHETBOUN
PhD student

Ana ACOSTA-MONTALVO
PhD student

Rebecca GOUTCHTAT
PhD student

Gianni PASQUETTI
PhD student

Mehdi MAANAOUI
PhD student

Maria MORENA
PhD student

Valentin LERICQUE
PhD student

Amaury D’HAUSSY
Master student

Mireia GOMEZ
Master student

Publications

Bonner C, Kerr-Conte J, Gmyr V, Queniat G, Moerman E, Thévenet J, Beaucamps C, Delalleau N, Popescu I, Malaisse WJ, Sener A, Deprez B, Abderrahmani A, Staels B, Pattou F.
Inhibition of the glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion.
Nat Med. 2015 May;21(5):512-7.

Lassailly G, Caiazzo R, Buob D, Pigeyre M, Verkindt H, Labreuche J, Raverdy V, Leteurtre E, Dharancy S, Louvet A, Romon M, Duhamel A, Pattou F, Mathurin P.
Bariatric Surgery Reduces Features of Nonalcoholic Steatohepatitis in Morbidly Obese Patients.
Gastroenterology. 2015 Aug;149(2):379-88.

Prévost G, Jeandel L, Arabo A, Coëffier M, El Ouahli M, Picot M, Alexandre D, Gobet F, Leprince J, Berrahmoune H, Déchelotte P, Malagon M, Bonner C, Kerr-Conte J, Chigr F, Lefebvre H, Anouar Y, Chartrel N.
Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis.
Diabetes. 2015 Aug;64(8):2805-16.

Saponaro C, Gmyr V, Thévenet J, Moerman E, Delalleau N, Pasquetti G, Coddeville A, Quenon A, Daoudi M, Hubert T, Vantyghem MC, Bousquet C, Martineau Y, Kerr-Conte J, Staels B, Pattou F, Bonner C.
The GLP1R Agonist Liraglutide Reduces Hyperglucagonemia Induced by the SGLT2 Inhibitor Dapagliflozin via Somatostatin Release.
Cell Rep. 2019 Aug 6;28(6):1447-1454.

Saponaro C, Mühlemann M, Acosta-Montalvo A, Piron A, Gmyr V, Delalleau N, Moerman E, Thévenet J, Pasquetti G, Coddeville A, Cnop M, Kerr-Conte J, Staels B, Pattou F, Bonner C.
Interindividual Heterogeneity of SGLT2 Expression and Function in Human Pancreatic Islets.
Diabetes. 2020 May;69(5):902-914.

Team contact

François Pattou
Unit director

françois.pattou@univ-lille.fr