Research summary
Molecular and physiological analysis of energy homeostasis in health and disease
Glucose homeostasis and development of type 2 diabetes are critically dependent on the capacity of the insulin secreting beta-cells of the pancreas to secrete insulin according to the metabolic need of the organism. This secretory capacity depends on both the number and secretion capacity of the differentiated beta-cells.
One of our research projects aimed at identying novel genes that regulate beta-cell proliferation, secretion capacity and apoptosis. To this end we are evaluating the mode of action on beta-cells of the gluco-incretin hormones GLP-1 and GIP, which are known to stimulate beta-cell precursor differentiation and proliferation of mature beta-cells, as well as to protect these cells against apoptosis. Our ongoing work was initiated by performing transcript profiling of islets from mice with genetic inactivation of the GLP-1 and GIP receptors, and which showed decreased secretion capacity and increased susceptibility to apoptosis. The function of these genes is investigated by overexpression or down-expression (siRNA) studies in beta-cell lines, primary beta cells and in transgenic mice, followed by functional analysis of proliferation, apoptosis, insulin secretion, as well as whole body glucose homeostasis.