title: Noninvasive in vivo model demonstrating the effects of autonomic innervation on pancreatic islet function.
abstract: The autonomic nervous system is thought to modulate blood glucose homeostasis by regulating endocrine cell activity in the pancreatic islets of Langerhans. The role of islet innervation, however, has remained elusive because the direct effects of autonomic nervous input on islet cell physiology cannot be studied in the pancreas. Here, we used an in vivo model to study the role of islet nervous input in glucose homeostasis. We transplanted islets into the anterior chamber of the eye and found that islet grafts became densely innervated by the rich parasympathetic and sympathetic nervous supply of the iris. Parasympathetic innervation was imaged intravitally by using transgenic mice expressing GFP in cholinergic axons. To manipulate selectively the islet nervous input, we increased the ambient illumination to increase the parasympathetic input to the islet grafts via the pupillary light reflex. This reduced fasting glycemia and improved glucose tolerance. These effects could be blocked by topical application of the muscarinic antagonist atropine to the eye, indicating that local cholinergic innervation had a direct effect on islet function in vivo. By using this approach, we found that parasympathetic innervation influences islet function in C57BL/6 mice but not in 129X1 mice, which reflected differences in innervation densities and may explain major strain differences in glucose homeostasis. This study directly demonstrates that autonomic axons innervating the islet modulate glucose homeostasis.
authors.affiliation: Diabetes Research Institute, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Rayner
authors.initials: R
authors.lastname: Rodriguez-Diaz
authors.forename: Stephan
authors.initials: S
authors.lastname: Speier
authors.forename: Ruth Damaris
authors.initials: RD
authors.lastname: Molano
authors.forename: Alexander
authors.initials: A
authors.lastname: Formoso
authors.forename: Itai
authors.initials: I
authors.lastname: Gans
authors.forename: Midhat H
authors.initials: MH
authors.lastname: Abdulreda
authors.forename: Over
authors.initials: O
authors.lastname: Cabrera
authors.forename: Judith
authors.initials: J
authors.lastname: Molina
authors.forename: Alberto
authors.initials: A
authors.lastname: Fachado
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Ingo
authors.initials: I
authors.lastname: Leibiger
authors.forename: Antonello
authors.initials: A
authors.lastname: Pileggi
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.forename: Alejandro
authors.initials: A
authors.lastname: Caicedo
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D005123:Eye / Q000294:innervation*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007498:Iris / Q000294:innervation / Q000502:physiology; D007515:Islets of Langerhans / Q000502:physiology*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009412:Nerve Fibers
chemical_list: D049452:Green Fluorescent Proteins