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Diabetes cellular and clinical pathogenesis

Diabetes is a disease that affects over 350 million people worldwide and its prevalence is increasing, including in emerging countries, a phenomenon related to the strong increase in overweight and obesity. Despite therapeutic advances, diabetes remains a major cause of kidney failure, blindness, amputations and cardiovascular diseases. The non- auto -immune or type 2 (T2DM ) diabetes is characterized by an impaired ability of muscle, liver and adipose tissue to respond to insulin (insulin resistance) combined with the inability of pancreatic beta cells to respond to glucose by increasing appropriately insulin secretion.

The project team focuses on the two main features of T2DM in order to understand the mechanisms involved in the development of insulin resistance in the liver, skeletal muscle and adipose tissue, and in the impaired insulin secretion by pancreatic beta cells . We study how lipids accumulate in the liver (steatosis and steatohepatitis) and muscles (production of ceramides) and disrupt insulin signaling. We also aim at understanding  the inflammatory pathways involved in the liver and adipose tissue of obese individuals, a mechanism that contributes to the local and global insulin resistance.

Concerning insulin secretion, we focus on factors (stress, hyperglycemia) and cellular mechanisms that modulate the capacity of the adult pancreas to secrete insulin. We particularly study the phenotype of atypical type of T2DM, ketosis prone T2DM and the role of viral infection in its onset. 

These studies are performed in cellular models (hepatocytes, muscle cells, adipocytes, pancreatic beta cells) in culture, in animal models of rodents, wild-type or transgenic, but also in humans due to the presence in the team of clinicians. Our findings allow us to explore new therapeutic approaches.




 Team Leader : Fabienne FOUFELLE (Dr)

Team Members : Olivier BOURRON (Pr), Jean-Michel DAVAINE (Dr), Eric HAJDUCH (Dr), Agnès HARTEMANN (Pr), , Marie LAGOUGE (Dr), Franck PHAN (Dr), Vlad RATZIU (Pr). 

Anne-Francoise BATTO (Tech), Nabiha BOUJARDINE (Eng), Isabelle HAINAULT (Eng), Kamel MELIANI (Tech), Sophie TAN (Eng).

Cécile BANDET (PhD), Valentova BARBORA (PhD), Menghue HU (PhD), Floriane LACHKAR (PhD) 

Administration : Valérie RESVE

Contact details: 33 1 44 27 24 31,  Email :

Selected Publications

  • Dalmas E, Toubal A, Alzaid F, Blazek K, Eames HL, Lebozec K, Pini M, Hainault I, Montastier E, Denis RG, Ancel P, Lacombe A, Ling Y, Allatif O, Cruciani-Guglielmacci C, André S, Viguerie N, Poitou C, Stich V, Torcivia A, Foufelle F, Luquet S, Aron-Wisnewsky J, Langin D, Clément K, Udalova IA, Venteclef N. Irf5 deficiency in macrophages promotes beneficial adipose tissue expansion and insulin sensitivity during obesity. Nat Med. 2015 Jun;21(6):610-8.
  • Bourron O, Caron-Debarle M, Hie M, Amoura Z, Andreelli F, Halbron M, Fonfrede M, Leroux G, Vigouroux C, Hartemann A. Type B Insulin-resistance syndrome: a cause of reversible autoimmune hypoglycaemia. Lancet. 2014 Oct 25;384(9953):1548.
  • Valtat B, Riveline JP, Zhang P, Singh-Estivalet A, Armanet M, Venteclef N, Besseiche A, Kelly DP, Tronche F, Ferré P, Gautier JF, Bréant B, Blondeau B. Fetal PGC-1alpha overexpression programs adult pancreatic ß-cell dysfunction. Diabetes. 2013 62:1206-16.
  • Blouin CM, Prado C, Takane KK, Lasnier F, Garcia-Ocana A, Ferré P, Dugail I, Hajduch E. Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling. Diabetes. 2010 Mar;59(3):600-10.
  • Kammoun HL, Chabanon H, Hainault I, Luquet S, Magnan C, Koike T, Ferré P, Foufelle F. GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice. J Clin Invest. 2009 119:1201-15.obngwi E, Choukem SP, Agbalika F, Blondeau B, Fetita LS, Lebbe C, Thiam D,  Cattan P, Larghero J, Foufelle F, Ferre P, Vexiau P, Calvo F, Gautier JF. Ketosis-prone type 2 diabetes mellitus and human herpesvirus 8 infection in sub-saharan africans. JAMA. 2008 299:2770-6.

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