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Metabolic Diseases, Diabetes and Co-morbidities

Principal investigator :
Fabienne FOUFELLE Ph.D.

Research team :

Anne-Françoise Bato, Bertrand Blondeau, Olivier Bourron, Jean-François Gautier, Ghislaine Guillemain, Isabelle Hainault, Eric Hajduch, Kamel Meliani, Valérie Resve.

[See all of Dr. Bourron’s videos here]

We study the physiopathology of type 2 diabetes. Our research is articulated around two topics which represent the two “arms” of diabetes: (i) insulin resistance in insulin sensitive tissues and (ii) physiopathology of insulin secretion of beta cells.

Insulin resistance (IR) is a condition in which normal amounts of insulin are inadequate to produce a normal insulin response in insulin-responsive tissues (fat, muscle and liver cells). IR is strongly associated with lipid overload and it is now accepted that the intracellular accumulation of lipids and lipid derivatives such as ceramides in insulin-responsive tissues other than adipose tissue (ectopic fat deposition) is responsible for the deterioration of insulin sensitivity. Under normal conditions, pancreatic ß-cells increase insulin release sufficiently to overcome the reduced efficiency of insulin action, thereby maintaining normal glucose tolerance. For type 2 diabetes appearance, ß-cells must be unable to compensate fully for the decreased insulin sensitivity. Therefore, an intrinsic failure of pancreatic ß cell is a prerequesite in the transition from insulin resistance to established type 2 diabetes.

In this context, the scientific project that we develop has three major objectives:
1. To identify the cellular and molecular mechanisms involved in lipid deposition and steatosis in the liver.
2. To determine the mechanisms involved in ceramide-induced insulin resistance in muscle cells.
3. To unravel the role of glucocorticoids and hyperglycemia in the foetal programming of type 2 diabetes.

We develop physiological approaches, primary cultures of rodent and human cells (liver, adipose tissue and muscles) and original animal models (transgenic, inducible knock-out and gene transfer by adenoviral strategies) to generate data that can be translated to humans.


This laboratory focuses on the mechanisms leading to type 2 diabetes, insulin resistance and defects of insulin secretion in animal models and in human subjects.




1. 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-1α Overexpression Programs Adult Pancreatic β-cell Dysfunction. Diabetes. 2013 in press.
2. Dentin R, Tomas-Cobos L, Foufelle F, Leopold J, Girard J, Postic C, Ferré P. Glucose 6-phosphate, rather than xylulose 5-phosphate, is required for the activation of ChREBP in response to glucose in the liver. J Hepatol. 2012; 56 :199-209.

3. Blouin CM, Prado C, Takane KK, Lasnier F, Garcia-Ocana A, Ferré P, Dugail I. and Hajduch E. Plasma membrane subdomain compartmentalization contributes to distinct mechanisms of ceramide action on insulin signaling. Diabetes 2010, 59: 600-610
4. Kammoun HL, Chabanon H, Hainault I, Luquet S, Magnan C, Koike T, Ferré P and 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

5. Sobngwi E, Choukem SP, Agbalika F, Blondeau B, Fetita LS, Lebbe C, Thiam D, Cattan P, Larghero J, Foufelle F, Ferré P, Vexiau P, Calvo F and Gautier JF. Ketosis-prone type 2 diabetes mellitus and human herpesvirus 8 infection in sub-saharan africans. JAMA 2008, 299:2770-6.