Abstract
Autonomic neurons innervate pancreatic islets of Langerhans and participate in the maintenance of blood glucose concentrations by controlling hormone levels through attachment with islet cells. We previously found that stimulated superior cervical ganglia (SCG) could induce Ca2+ oscillation in α cells via neuropeptide substance P using an in vitro co-culture model. In this study, we studied the effect of SCG neurite adhesion on intracellular secretory granule movement and glucagon secretion in α cells stimulated by low glucose concentration. Spinning disk microscopic analysis revealed that the mean velocity of intracellular granules was significantly lower in α cells attached to SCG neurites than that in those without neurites under low (2 mM), middle (10 mM), and high (20 mM) glucose concentrations. Stimulation by a low (2 mM) glucose concentration significantly increased glucagon secretion in α cells lacking neurites but not in those bound to neurites. These results suggest that adhesion to SCG neurites decreases low glucose-induced glucagon secretion in pancreatic α cells by attenuating intracellular granule movement activity.
This is a preview of subscription content, log in via an institution to check access.
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
References
Gylfe E (2016) Glucose control of glucagon secretion: ‘There’s a brand-new gimmick every year’. Ups J Med Sci 121:120–132
Ahrén B (2000) Autonomic regulation of islet hormone secretion—implications for health and disease. Diabetologia 43:393–410
Lindsay TH, Halvorson KG, Peters CM et al (2006) A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas. Neuroscience 137:1417–1426
Chiu YC, Hua TE, Fu YY et al (2012) 3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury. Diabetologia 55:3252–3261
Di Cairano ES, Moretti S, Marciani P et al (2006) Neurotransmitters and neuropeptides: new players in the control of islet of Langerhans’ cell mass and function. J Cell Physiol 231:756–767
Brereton MF, Vergari E, Zhang Q, Clark A (2015) Alpha-, Delta- and PP-cells: are they the architectural cornerstones of islet structure and co-ordination? J Histochem Cytochem 63:575–591
Rodriguez-Diaz R, Menegaz D, Caicedo A (2014) Neurotransmitters act as paracrine signals to regulate insulin secretion from the human pancreatic islet. J Physiol 592:3413–3417
Rodriguez-Diaz R, Abdulreda MH, Formoso AL et al (2011) Innervation patterns of autonomic axons in the human endocrine pancreas. Cell Metab 14:45–54
Koma Y, Furuno T, Hagiyama M et al (2008) Cell adhesion molecule 1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactions. Gastroenterology 134:1544–1554
Nakamura M, Inoh Y, Nakanishi M, Furuno T (2013) Substance P plays an important role in cell adhesion molecule 1-mediated nerve-pancreatic islet α cell interaction. Biochem Biophys Res Commun 438:563–567
Yokawa S, Furuno T, Suzuki T et al (2016) Effect of cell adhesion molecule 1 expression on intracellular granule movement in pancreatic α cells. Cell Biochem Biophys 74:391–398
Suzuki R, Furuno T, McKay DM et al (1999) Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P. J Immunol 163:2410–2415
Heaslip AT, Nelson SR, Lombardo AT et al (2014) Cytoskeletal dependence of insulin granule movement dynamics in INS-1 beta-cells in response to glucose. PLoS ONE 9:e109082
Nelson SR, Ali MY, Trybus KM, Warshaw DM (2009) Random walk of processive, quantum dot-labeled myosin Va molecules within the actin cortex of COS-7 cells. Biophys J 97:509–518
Saxton MJ (1997) Single-particle tracking: the distribution of diffusion coefficients. Biophys J 72:1744–1753
Yoshimatsu H, Niijima A, Oomura Y et al (1984) Effects of hypothalamic lesion on pancreatic autonomic nerve activity in the rat. Brain Res 303:147–152
Rossi J, Santamäki P, Airaksinen MS, Herzig KH (2005) Parasympathetic innervation and function of endocrine pancreas requires the glial cell line-derived factor family receptor alpha2 (GFRalpha2). Diabetes 54:1324–1330
Borden P, Houtz J, Leach SD, Kuruvilla R (2013) Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation. Cell Rep 4:287–301
Gromada J, Franklin I, Wollheim CB (2007) α-Cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev 28:84–116
Gylfe E, Gilon P (2014) Glucose regulation of glucagon secretion. Diabetes Res Clin Pract 103:1–10
Gylfe E, Tengholm A (2014) Neurotransmitter control of islet hormone pulsatility. Diabetes Obes Metab 16:102–110
Röder PV, Wong X, Hong W, Han W (2016) Molecular regulation of insulin granule biogenesis and exocytosis. Biochem J 473:2737–2756
Zhang M, March ME, Lane WS, Long EO (2014) A signaling network induced by β2 integrin controls the polarization of lytic granulesin cytotoxic cells. Sci Signal 7:ra96
Mundinger TO, Mei Q, Figlewicz DP et al (2003) Impaired glucagon response to sympathetic nerve stimulation in the BB diabetic rat: effect of early sympathetic islet neuropathy. Am J Physiol Endocrinol Metab 285:E1047–1054
Zhang C, Caldwell TA, Mirbolooki MR et al (2016) Extracellular CADM1 interactions influence insulin secretion by rat and human islet β-cells and promote clustering of syntaxin-1. Am J Physiol Endocrinol Metab 310:E874–E885
Acknowledgements
We thank Mr. Atsuhiro Shinohara, Mr. Ryosuke Oguri, and Mr. Takanari Ikeda (Aichi Gakuin University) for basic experiments. This was supported by grants from the Japan Society for the Promotion of Sciences Kakenhi Grant Nos. (26440083 and 17K07374 to TF).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
11010_2018_3275_MOESM1_ESM.avi
Video 1—Intracellular granule movement of αTC1.6 cells corresponding to Fig. 1a. Images were acquired at two frames/s for 120 s under high glucose concentration (20 mM). The movie plays at 20× speed (AVI 61737 KB)
11010_2018_3275_MOESM2_ESM.avi
Video 2—Intracellular granule movement of αTC1.6 cells attached to neurites corresponding to Fig. 1b. Images were acquired at two frames/s for 120 s under high glucose concentration (20 mM). The movie plays at 20× speed (AVI 61737 KB)
Rights and permissions
About this article
Cite this article
Watabe, K., Yokawa, S., Inoh, Y. et al. Decreased intracellular granule movement and glucagon secretion in pancreatic α cells attached to superior cervical ganglion neurites. Mol Cell Biochem 446, 83–89 (2018). https://doi.org/10.1007/s11010-018-3275-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-018-3275-2