Team Stéphane DALLE – Eric RENARD
Innovative therapeutics for diabetes
The aim of the “Innovative therapeutics for diabetes” team is to develop fundamental, translational and clinical research to improve the treatment of diabetes in its various clinical and pathophysiological forms based on multidisciplinary expertise. The team composed of researchers, research professor, hospital practitioners and engineers, is working to develop new therapeutic strategies aimed at correcting, restoring or preserving the insulin secretory function of pancreatic beta cells in diabetes.
Human islet (insulin : green ; glucagon : red)
Histological section of mouse pancreas showing an inflammatory reaction
IGF Sud 119
04 34 35 92 03
IGF Sud 001 04 67 33 83 82
IGF Sud 119 04 34 35 92 03
IGF Sud 119 04 34 35 92 03
IGF Sud 119 04 34 35 92 03
IGF Sud 119 04 34 35 92 03
IGF Sud 119 04 34 35 92 03- Reznik Y, Carvalho M, Fendri S, Prevost G, Chaillous L, Riveline JP, Hanaire H, Dubois S, Houéto P, Pasche H, Mianowska B, Renard E. Should people with type 2 diabetes treated by multiple daily insulin injections with home health care support be switched to hybrid closed-loop? The CLOSE AP+ randomized controlled trial. Diabetes Obes Metab. 2024 Feb;26(2):622-630. doi: 10.1111/dom.15351. PMID: 37921083
- Diallo A, Villard O, Carlos-Bolumbu M, Renard E, Galtier F. Effects of hypoglycaemic agents on reducing surrogate metabolic parameters for the prevention of cardiovascular events and death in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Obes Metab. 2024 Feb;26(2):495-502. doi: 10.1111/dom.15335. PMID: 37869934
- Renard E, Joubert M, Villard O, Dreves B, Reznik Y, Farret A, Place J, Breton MD, Kovatchev BP; iDCL Trial Research Group. Safety and Efficacy of Sustained Automated Insulin Delivery Compared With Sensor and Pump Therapy in Adults With Type 1 Diabetes at High Risk for Hypoglycemia: A Randomized Controlled Trial. Diabetes Care. 2023 Dec 1;46(12):2180-2187. doi: 10.2337/dc23-0685. PMID: 37729080
- Zaïmia N, Obeid J, Varrault A, Sabatier J, Broca C, Gilon P, Costes S, Bertrand G, Ravier MA. GLP-1 and GIP receptors signal through distinct b-arrestin 2-dependent pathways to regulate pancreatic b cell function. Cell Rep. 2023 Nov28;42(11):113326. doi: 10.1016/j.celrep.2023.113326. PMID: 37897727
- Coutant R, Bismuth E, Bonnemaison E, Dalla-Vale F, Morinais P, Perrard M, Trely J, Faure N, Bouhours-Nouet N, Levaillant L, Farret A, Storey C, Donzeau A, Poidvin A, Amsellem-Jager J, Place J, Quemener E, Hamel JF, Breton MD, Tubiana-Rufi N, Renard E. Hybrid Closed Loop Overcomes the Impact of Missed or Suboptimal Meal Boluses on Glucose Control in Children with Type 1 Diabetes Compared to Sensor-Augmented Pump Therapy. Diabetes Technol Ther. 2023 Jun;25(6):395-403. doi: 10.1089/dia.2022.0518. PMID: 36927054
- Dalle S, Abderrahmani A, Renard E. Pharmacological inhibitors of beta-cell dysfunction and death as therapeutics for Diabetes. Front Endocrinol. 2023 Mar 15;14:1076343. doi: 10.3389/fendo.2023.1076343. eCollection 2023. PMID: 37008937
- Brown MR, Laouteouet D, Delobel M, Villard O, Broca C, Bertrand G, Wojtusciszyn A, Dalle S, Ravier MA, Matveyenko AV, Costes S. The nuclear receptor REV-ERBα is implicated in the alteration of β-cell autophagy and survival under diabetogenic conditions. Cell Death Dis. 2022 Apr 15;13(4):353. doi: 10.1038/s41419-022-04767- PMID: 35428762
- Renard E, Tubiana-Rufi N, Bonnemaison E, Coutant R, Dalla-Vale F, Bismuth E, Faure N, Bouhours-Nouet N, Farret A, Storey C, Donzeau A, Poidvin A, Amsellem-Jager J, Place J, Breton MD; Free-life Kid AP Study Group. Outcomes of hybrid closed-loop insulin delivery activated 24/7 versus evening and night in free-living prepubertal children with type 1 diabetes: A multicentre, randomized clinical trial. Diabetes Obes Metab. 2022 Mar;24(3):511-521. doi: 10.1111/dom.14605. PMID: 34816597
- Costes S, Bertrand G, Ravier MA. Mechanisms of Beta-Cell Apoptosis in Type 2 Diabetes-Prone Situations and Potential Protection by GLP-1-Based Therapies. Int J Mol Sci. 2021 May 18;22(10):5303. doi: 10.3390/ijms22105303. PMID: 34069914
- Ruiz L, Gurlo T, Ravier MA, Wojtusciszyn A, Mathieu J, Brown MR, Broca C, Bertrand G, Butler PC, Matveyenko AV, Dalle S, Costes S. Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment. Cell Death Dis. 2018 May 22;9(6):600. doi: 10.1038/s41419-018-0603-0. PMID: 29789539
- Leduc M, Richard J, Costes S, Muller D, Varrault A, Compan V, Mathieu J, Tanti JF, Pagès G, Pouyssegur J, Bertrand G, Dalle S, Ravier MA. ERK1 is dispensable for mouse pancreatic beta cell function but is necessary for glucose-induced full activation of MSK1 and CREB. Diabetologia. 2017 Oct;60(10):1999-2010. doi: 10.1007/s00125-017-4356-6. PMID: 28721437
- Varin EM, Wojtusciszyn A, Broca C, Muller D, Ravier MA, Ceppo F, Renard E, Tanti JF, Dalle S. Inhibition of the MAP3 kinase Tpl2 protects rodent and human beta-cells from apoptosis and dysfunction by cytokines and enhances anti-inflammatory actions of exendin-4. Cell Death Dis. 2016 Jan 21;7(1):e2065. doi: 10.1038/cddis.2015.399. PMID: 26794660
Mechanisms of beta-cell alteration: involvement of amyloidogenic proteins and pesticides
Principal investigator
Safia COSTES
Inflammatory and metabolic stress of the pancreatic beta cell
Principal investigator
Stéphane DALLE
Automated insulin delivery by wearable or implantable systems
Principal investigator
Eric RENARD
Clinical development in diabetology: from cell therapy to new technologies
The clinical research projects of the Endocrinology-Diabetology Department at Montpellier University Hospital aim to develop:
- New technological modalities of insulin therapy for patients with diabetes in complex glycemic control situations such as gastroparesis, end-stage renal failure, or patients treated with multi-daily insulin injection. Our aim is to use continuous glucose measurement to optimize insulin therapy and make it accessible to all patients, including the most complicated.
- Cell therapy for diabetes, with an expertise on the isolation of human pancreatic islets (PRISM platform) and islet transplantation for patients with diabetes and high glycemic variability, hypoglycemia unawareness jeopardizing their quality of life and vital prognosis.
Current projects include:
• Evaluation of the efficacy of automated insulin delivery in patients with diabetes on hemodialysis: a randomized cross-over pilot study (AUTO-HEMODIAB)
• Real-life randomized controlled trial evaluating the effect of endoscopic pylorotomy by gastric POEM on glycemic control in patients with diabetes and gastroparesis (DIAPOEM)
• Evaluation of the performance and safety of the EkiYou Dose V2 application in patients with diabetes treated with multiple insulin injections
• Effect of islet transplantation on the incidence of diabetic complications and mortality in
type 1 diabetic patients (CPL-ILOT).
• Auto-islet transplantation in total pancreatoduodenectomy for benign disease of the duodenopancreas
IGF staff involved
Eric RENARD
PUPH, University of Montpellier
Orianne VILLARD
CC-AH University of Montpellier
Bader Al Taweel
CC Université de Montpellier
Anne FARRET
PH, Montpellier University Hospital
Publications
• Renard E., et al (2023) Diabetes Care, 46
• Villard O., et al. (2022) Diabetes Care, 45
• Lablanche S., et al (2021) Am J Transplant
Collaborations
• Antoine Debourdeau (Montpellier)
• Omar Diouri (Montpellier)
• Sandrine Lablanche (Grenoble)
• Marc Breton (Charlottesville)
Funding
• 2023-2025 : Société Francophone du Diabète (SFD 2023)
• 2023-2025 : Appel d’Offre Tremplin (CHU de Montpellier)
• 2023-2025 : Fonds Agir pour les Maladies Chroniques
• 2023-2024 : Adène Fonds de dotation
• 2023 : Prix de l’Innovation Numérique Diabète (Sanofi)
