AGATE

The aim of the project, which was established at the beginning of 2000 and is planned to run for 15 years, is the characterization of endocrine processes under chronobiological aspects, whereby the influence of pineal melatonin on secretion rhythm and signal transduction processes of the Langerhans Isle is at the centre of the investigations. Prerequisite for the project approval were in vitro findings, which for the first time showed the existence of conflicting influences of closely related indo-lamines (melatonin and serotonin) on insulin secretion. Subsequent investigations showed that the insulin secretion of isolated pancreatic islands follows a circadian rhythm and that melatonin is a potent hydroxyl radical scavenger. Furthermore, physiological, autoradiographic and molecular-biological investigations have confirmed that the insulin-producing ß-cell has melatonin (MT1) receptors and that the intracellular signal transduction cascade is via the adenylate cyclase/cAMP system. In the future, studies on the expression of melatonin receptors in the daily course, the expression of contemporary genes and the verification of in vitro results by in vivo studies will follow, which could bridge the gap to the clinical relevance and significance of melatonin for diabetogenesis.