|An Integrated Network of Glucose Sensing Cells in Glucose Homeostasis
Domaine: ERC Advanced Grant
Durée: 01.08.2011 - 31.07.2016 (à confirmer)
Budget total: 2.499.421 EUR
Glucose homeostasis is controlled by an integrated network of glucose sensing cells, located at several anatomical sites, and which control glucose utilization, endogenous glucose production, energy expenditure, and feeding behavior. The coordination by glucose of these functions depends on secretion of the hormones insulin and glucagon and on the control by the autonomic nervous system of the endocrine pancreas and of the major organs involved in glucose homeostasis: liver, fat and muscle.
Obesity and diabetes can be considered as a consequence of impaired glucose sensing leading to deregulated secretion of pancreatic hormones and abnormal regulation of the autonomic nervous system. Here, we propose an investigative and discovery program to provide new knowledge on three aspects of this integrated glucose sensing network using molecular biology, genetic, genomic and integrated physiological studies in animal models.
Specifically, we will:
- 1) identify novel mechanisms controlling the glucose competence, proliferation and protection against apoptosis of pancreatic beta-cells, the central node of this integrated glucose sensing network;
- 2) identify how brain glucose sensors, that are functionally similar to pancreatic beta-cells, control glucose homeostasis and islet function and mass;
- 3) undertake a genetic-genomic discovery program to identify genetic loci and genes involved in central hypoglycemia detection and the control of counterregulation, a process poorly understood and whose deregulation is the major problem in insulin treatment of both type 1 and type 2 diabetes.
Together these investigations will bring novel information critical for the development of novel therapeutic approach to major metabolic diseases.