Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 52, Pages 21456-21461Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1211659110
Keywords
diabetes; beta cell; alpha cell; insulin; glucagon
Categories
Funding
- Diabetes Research Institute Foundation
- National Institutes of Health [R56DK084321, R01DK084321, 5U19AI050864-10, F32DK083226, U-01 DK 089538]
- Juvenile Diabetes Research Foundation [3-2007-73]
- European Foundation
- Strategic Research Program in Diabetes at Karolinska Insitutet
- Skandia Insurance Company, Ltd.
- Berth von Kantzow's Foundation
- Knut and Alice Wallenberg Foundation
- VIBRANT [FP7-228933-2]
- Swedish Research Council
- Novo Nordisk Foundation
- Swedish Diabetes Association
- Family Erling-Persson Foundation
- Soderbergs Foundation
- Stichting af Jochnick Foundation
- World Class University Program through the National Research Foundation of Korea
- Ministry of Education, Science and Technology [R31-2008-000-10105-0]
- Novo Nordisk Fonden [NNF12OC1016557] Funding Source: researchfish
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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.
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