| 1. |
- Rodriguez-Diaz, R, et al.
(författare)
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Noninvasive in vivo model demonstrating the effects of autonomic innervation on pancreatic islet function
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:52, s. 21456-21461
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Cabrera, O, et al.
(författare)
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Automated, High-Throughput Assays for Evaluation of Human Pancreatic Islet Function
- 2007
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Ingår i: Cell transplantation. - : SAGE Publications. - 1555-3892 .- 0963-6897. ; 16:10, s. 1039-1048
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Tidskriftsartikel (refereegranskat)abstract
- An important challenge in pancreatic islet transplantation in association with type 1 diabetes is to define automatic high-throughput assays for evaluation of human islet function. The physiological techniques presently used are amenable to small-scale experimental samples and produce descriptive results. The postgenomic era provides an opportunity to analyze biological processes on a larger scale, but the transition to high-throughput technologies is still a challenge. As a first step to implement high-throughput assays for the study of human islet function, we have developed two methodologies: multiple automated perifusion to determine islet hormone secretion and high-throughput kinetic imaging to examine islet cellular responses. Both technologies use fully automated devices that allow performing simultaneous experiments on multiple islet preparations. Our results illustrate that these technologies can be applied to study the functional status and explore the pharmacological profiles of islet cells. These methodologies will enable functional characterization of human islet preparations before transplantation and thereby provide the basis for the establishment of predictive tests for β-cell potency.
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| 5. |
- Molina, J, et al.
(författare)
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Control of insulin secretion by cholinergic signaling in the human pancreatic islet
- 2014
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 63:8, s. 2714-2726
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Tidskriftsartikel (refereegranskat)abstract
- Acetylcholine regulates hormone secretion from the pancreatic islet and is thus crucial for glucose homeostasis. Little is known, however, about acetylcholine (cholinergic) signaling in the human islet. We recently reported that in the human islet, acetylcholine is primarily a paracrine signal released from α-cells rather than primarily a neural signal as in rodent islets. In this study, we demonstrate that the effects acetylcholine produces in the human islet are different and more complex than expected from studies conducted on cell lines and rodent islets. We found that endogenous acetylcholine not only stimulates the insulin-secreting β-cell via the muscarinic acetylcholine receptors M3 and M5, but also the somatostatin-secreting δ-cell via M1 receptors. Because somatostatin is a strong inhibitor of insulin secretion, we hypothesized that cholinergic input to the δ-cell indirectly regulates β-cell function. Indeed, when all muscarinic signaling was blocked, somatostatin secretion decreased and insulin secretion unexpectedly increased, suggesting a reduced inhibitory input to β-cells. Endogenous cholinergic signaling therefore provides direct stimulatory and indirect inhibitory input to β-cells to regulate insulin secretion from the human islet.
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