title: Melatonin-receptor-1-deficiency affects neurogenic differentiation factor immunoreaction in pancreatic islets and enteroendocrine cells of mice.
abstract: Neurogenic differentiation factor (NeuroD) is a transcription factor involved in the differentiation of neurons and in the control of energy balance and metabolism. It plays a key role in type 1 and type 2 diabetes. Melatonin is an important rhythmic endocrine signal within the circadian system of mammals and modulates insulin secretion and glucose metabolism. In the mouse pars tuberalis, NeuroD mRNA levels show day/night variation, which is independent of the molecular clock gene mPER1 but depends on the functional melatonin receptor 1 (MT1). So far, little is known about the effect of melatonin on NeuroD synthesis in the gastrointestinal tract. Thus, NeuroD protein levels and cellular localization were analyzed by immunohistochemistry in pancreatic islets and duodenal enteroendocrine cells of MT1- and mPER1-deficienct mice. In addition, the localization of NeuroD-positive cells was analyzed by double-immunofluorescence and confocal laser microscopy. In duodenal enteroendocrine cells and pancreatic islets of WT and PER1-deficient mice, NeuroD immunoreaction showed a peak during the early subjective night. In contrast, this peak was absent in MT1-deficent mice. These data suggest that melatonin, by acting on MT1 receptors, affects NeuroD expression in the gastrointestinal tract and thus might contribute to circadian regulation in metabolic functions.
authors.affiliation: Dr. Senckenbergische Anatomie, Institut für Anatomie II, Johann-Wolfgang-Goethe-Universität, Theodor-Stern-Kai 7, 60590, Frankfurt/M, Germany.
authors.forename: Andree
authors.initials: A
authors.lastname: Shalabi
authors.forename: Claudia
authors.initials: C
authors.lastname: Fischer
authors.forename: Horst-Werner
authors.initials: HW
authors.lastname: Korf
authors.forename: Charlotte
authors.initials: C
authors.lastname: von Gall
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D004386:Duodenum / Q000166:cytology / Q000378:metabolism*; D019858:Enteroendocrine Cells / Q000166:cytology / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008550:Melatonin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D044122:Receptor, Melatonin, MT1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D008550:Melatonin; D009419:Nerve Tissue Proteins; D056950:Period Circadian Proteins; D044122:Receptor, Melatonin, MT1; C539023:Per1 protein, mouse; C093564:Neurogenic differentiation factor 1