Diabetes is the most prevalent metabolic disease in developed countries and one that engenders - in addition to its high fatality - enormous health care costs. The physiological meaning of the ‘feel-good’ hormone serotonin in insulin-producing cells of the pancreas was not understood for more than 40 years but has finally been resolved by scientists of the Max Planck Institute of Molecular Genetics in Berlin. The researchers Diego J. Walther, Nils Paulmann and colleagues report in the current issue of PloS Biology, that a lack of serotonin in the pancreas causes diabetes. The interdisciplinary research team identified the underlying molecular and physiological mechanisms. The close interdisciplinary collaboration with Marjan Rupnik, head of the Institute of Physiology in Maribor, Slovenia, and a former group leader at the Max Planck Institute for Biophysical Chemistry, as well as the collaboration with Heidrun Fink, executive director of the Institute of Pharmacology and Toxicology of the School of Veterinary Medicine, Free University Berlin, was particularly instrumental to allowed untangling these findings (Paulmann et al., PloS Biology, October 27, 2009). Prior studies of the team from Berlin have identified a novel mechanism of serotonin’s action in blood platelets that relies on the permanent covalent coupling of the hormone to signalling proteins, the so-called ‘serotonylation’. The scientists now identified this mechanism also in ?-cells of the pancreas. As in thrombocytes, serotonylation regulates the secretion of storage granules from these cells. "Under normal conditions serotonin controls the release of insulin, the most important hormone in the regulation of blood glucose concentration of humans and animals", explains Diego Walther. When the serotonin levels are low like in serotonin-deficient mice, proper insulin secretion is hampered and blood glucose concentration rises to noxious levels after a meal, a hallmark of diabetes. The identification of the insulin-releasing action of serotonin opens new avenues for intervention in diabetes, a main research objective for further studies by the international team.
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