THE CASE STUDY OF NESFATIN-1 IN PANCREAS: TURSIOPS AS NEW ANIMAL MODEL

In 2006 a new regulating molecule involved in food behavior called nesfatin–1 was identified [1]. Besides its central action as anorexigenic peptide, current data suggest that nesfatin-1 is a pleiotropic molecule involved in several regulatory processes in peripheral organs and tissues [2]. In particular, it has been shown that in pancreas of rodents and human, nesfatin-1 is localized in the β-cells and promotes the release of insulin. This raises the possibility that the dysfunction of the nesfatin-1 could be implicated in metabolic disorders, particularly in type 2 diabetes mellitus (T2D) [3]. Although various animal models have been used to study diabetes, a single species that fully complements T2D in humans has not been identified [4]. Recently, it has been discovered that dolphins have a prolonged glucose tolerance curve and during fasting maintain a state of hyperglycemia similar to human T2D [5]. The similarities between dolphins and human have led to the possibility of being able to consider dolphins as models for the studies at both physiological and pathological human behaviors. To this aim we decided to characterize nesfatin-1 distribution in pancreas of bottlenose dolphin (Tursiops truncatus) and evaluate pre and post-prandial blood levels of this molecule. Pancreas samples were receveid from the Mediterranean marine mammal tissue bank of the University of Padova while blood samples were provided by different Aquariums during routine veterinary controls. We carried out immunohistochemistry against nesfatin-1. We found that nesfatin-ImmunoReactive (IR) cells were distributed in pancreatic islets of Langerhans. In addition, by double immunofluorescence we discovered that nesfatin-1 never co-localizes with insulin-IR cells but with some glucagon-IR cells in the pancreatic islet. The specificity of nesfatin-1 antibody was confirmed by western-blot on homogenates of pancreas. We also evaluated plasma nesfatin-1 levels through ELISA analysis: we didn’t find a significant difference among samples comparing fasting and post-prandial states. We hypothesized that in dolphins nesfatin-1, due to its localization in α-cells, can stimulate glucagon secretion in order to maintain high blood sugar levels. In conclusion, our report adds novel information on the presence and distribution of nesfatin-1 in the pancreas of bottlenose dolphins. These results emphasize some common features between bottlenose dolphin and terrestrial mammals. More research is needed to fully understand the role that research on dolphins can play in understanding T2D in humans. [1] Oh-I S et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus, Nature 443:709- 712, 2006. [2] Prinz P et al. Expression and regulation of peripheral NUCB2/nesfatin-1, Curr Opin Pharmacol 31:25-30, 2016. [3] Gonzalez R et al. Pancreatic beta cells colocalize insulin and pronesfatin immunoreactivity in rodents, BiochemBiophys Res Commun 381:643-648, 2009. [4] Cefalu WT Animal models of type 2 diabetes: clinical presentation and pathophysiological relevance to the human condition, Ilar J 47:186-198, 2006. [5] Venn-Watson S et al. Dolphins as animal models for type 2 diabetes: Sustained, post-prandial hyperglycemia and hyperinsulinemia, Gener and Compar Endocrin 170:193-199, 2010.