Glucose homeostasis is maintained through tight regulation of glucose utilization, glucose production, and feeding behavior. These processes are regulated by hormonal and nervous signals that are produced in response to fluctuations in blood glucose concentrations. The production of these regulatory signals, as well as the control of inter-organ glucose fluxes are controlled, in large part, by the activity and regulated expression of a family of plasma membrane glucose transporters. Understanding in detail their structure, function, and regulated expression is critical to develop novel therapeutic strategies to treat metabolic diseases.
As a postdoctoral fellow in the laboratory of Harvey Lodish at the Whitehead Institute for Biomedical Research, Thorens cloned and characterized the pancreatic beta-cell glucose transporter Glut2. He determined its role in the glucose sensing mechanism of these cells. Since he moved back to Lausanne, he showed that this transporter is also required for glucose-activation of neuronal circuits controlling the secretion of glucagon in response to hypoglycemia, and the control of feeding and energy expenditure through a regulation of the hypothalamic melanocortin pathway. These studies led to the important notion that glucose homeostasis is controlled by a network of interacting glucose sensing cells located at different anatomical sites.
Novel members of the glucose transporter family have also been cloned and characterized in his laboratory, Glut8, a glucose transporter expressed in brain and in insulin sensitive tissues, and HMIT (SLC2A13), a H+/myo-inositol co-transporter expressed mostly in neurons and glial cells. More recently, he established a mouse model of hyperuricemia with uric acid crystal formation, by systemic or liver-specific knockout of Glut9 (SLC2A9), a gene associated with deregulated uric acid homeostasis and gout in humans.
This group has also established a state-of-the art core facility for the study of the function of membrane transporters in glucose and energy homeostasis. Studies related to TransCure will explore the role of Glut9 in the control of uricemia and the impact of deregulated uric acid plasma concentrations in the development of the metabolic syndrome. Studies are also focusing on the physiological importance of Glut8 in brain and muscle glucose metabolism and future work will investigate the role of HMIT in brain function.
Function in NCCR
- Principal Investigator / Member of the Management Committee
Professor of Physiology at the Department of Physiology and Center for Integrative Genomics, University of Lausanne
- Ph.D. in Sciences at the University of Geneva
- M.Sc. in Biochemistry at the University of Geneva
- Chairman of the Steering Committee, National Research Program on Stem Cells and Regenerative Medicine (NRP63), Switzerland
- Member of Review Committee, Agence Nationale de la Recherche (Physiology), France
- Programme National de Recherche sur le diabète, France, President of the Scientific Advisory Board
- Albert Renold Award of the European Association for the Study of Diabetes (2009)
- Cloëtta Award, Foundation Pr. Dr. Max Cloëtta (2002)
- Sarda Farriol Award, Sarda Farriol Foundation, Barcelona, Spain (1999)
- Friedrich Miescher Award of the Swiss Biochemical Society (1995)