Effect of Oxytocin on Cytosolic Calcium Concentration of Alpha and Beta Cells in Pancreas
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Effect of Oxytocin on Cytosolic Calcium Concentration of Alpha and Beta Cells in Pancreas

Authors: Rauza Sukma Rita, Katsuya Dezaki, Yuko Maejima, Toshihiko Yada


Oxytocin is a nine-amino acid peptide synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Oxytocin promotes contraction of the uterus during birth and milk ejection during breast feeding. Although oxytocin receptors are found predominantly in the breasts and uterus of females, many tissues and organs express oxytocin receptors, including the pituitary, heart, kidney, thymus, vascular endothelium, adipocytes, osteoblasts, adrenal gland, pancreatic islets, and many cell lines. On the other hand, in pancreatic islets, oxytocin receptors are expressed in both α-cells and β-cells with stronger expression in α- cells. However, to our knowledge there are no reports yet about the effect of oxytocin on cytosolic calcium reaction on α and β-cell. This study aims to investigate the effect of oxytocin on α-cells and β-cells and its oscillation pattern. Islet of Langerhans from wild type mice were isolated by collagenase digestion. Isolated and dissociated single cells either α-cells or β-cells on coverslips were mounted in an open chamber and superfused in HKRB. Cytosolic concentration ([Ca2+]i) in single cells were measured by fura-2 microfluorimetry. After measurement of [Ca2+]i, α-cells were identified by subsequent immunocytochemical staining using an anti-glucagon antiserum. In β-cells, the [Ca2+]i increase in response to oxytocin was observed only under 8.3 mM glucose condition, whereas in α-cells, [Ca2+]i an increase induced by oxytocin was observed in both 2.8 mM and 8.3 mM glucose. The oscillation incidence was induced more frequently in β-cells compared to α-cells. In conclusion, the present study demonstrated that oxytocin directly interacts with both α-cells and β-cells and induces increase of [Ca2+]i and its specific patterns.

Keywords: α-cells, β-cells, cytosolic calcium concentration, oscillation, oxytocin.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1129734

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[1] Z.R. Donaldson & L.J. Yong, “Oxytocin, vasopressin, and the neurogenetics of sociality,” Science, vol. 322, pp.900-904, Nov. 2008.
[2] A. Kiss, J.D. Mikkelsen, “Oxytocin-anatomy and functional assignments: a mini-review,” Endocr Regul, vol 39, pp.97-105, Sep.2005.
[3] N. Deblon, C. V-Durebex, L. Bourgoin, A. Caillon, A-L. Bussier, S Petrosino, F. Piscitelli, J.J. Legros, V. Geenen, M. Foti, W. Wahli, V.D. Marzo, and F.R. Jeanrenaud, “Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats,” PloS One, 6: e25565, Sept. 2011.
[4] G.J. Morton, B.S. Thatcher, R.D. Reidelberger, K. Ogimoto, T.W. Hanson, D. G. Baskin, M.W. Schwartz, and J.E. Blevins,” Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats,” Am J Physiol Endocrinol Metab, vol. 302, E134-144, Jan. 2012.
[5] G. Zhang, H. Bai, Zhang H, C. Dean, Q. Wu, J. Li, S. Guariglia, Q. Meng, and D. Cai, “Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance.,” Neuron, vol 69, pp 523-535, Feb. 2011.
[6] H. Suplicy, C. L. Boguszewski, C.M.C. Dos Santos, M.d.D.d. Figueiredo, D.R. Cunha, R. Radominski, “A comparative study of five centrally acting drugs on the pharmacological treatment of obesity,” International Journal of Obesity, vol 38, pp 1097-1103, Jan.2014.
[7] M. Kosfeld, M. Heinrichs, P. J. Zak, U. Fischbacher, E. Fehr, “Oxytocin increases trust in humans,” Nature, vol 435, pp 673-676, June.2005.
[8] I. D. Neumann & R. Landgraf, “Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors,” Trends in Neuroscience, vol 35, pp 649-659, Nov. 2012.
[9] R. Feldman, A. Weller, O. Z. Sharon, A. Levine, “Evidence for a neuroendocrinological foundation of human affiliation: plasma oxytocin levels across pregnancy and the postpartum period predict mother-infant bonding,” Psychol Sci, vol 18, pp 965-70, Nov. 2007.
[10] D. Jin, H.X. Liu, H. Hirai, T.Torashima, T. Nagai, O. Lopatina,N. A. Shnayder, K. Yamada, M. Noda, T. Seike, K. Fujita, S. Takasawa, S. Yokoyama, K. Koizumi, Y. Shiraishi, S. Tanaka, M. Hashii, T. Yoshihara, K. Higashida, M. S. Islam, N. Yamada, K. Hayashi, N. Noguchi, I. Kato, H. Okamoto, A. Matsushima, A. Salmina, T. Munesue, N. Shimizu, S. Mochida, M. Asano, H. Higashida, “CD38 is critical for social behaviour by regulating oxytocin secretion,” Nature, vol 446, 42-45, Feb. 2007.
[11] Y. Maejima, R.S.Rita, P. Santoso, M. Aoyama, Y. Hiraoka, K. Nishimori, D. Gantulga, K. Shimomura, T. Yada, “Nasal Oxytocin administration reduces food intake without affecting locomotor activity and glycemia with c-Fos induction in limited brain areas,” Neuroendocrinology, vol 5 (101), pp 35-44, Jan. 2015.
[12] H. Zhang, C. Wu, Q. Chen, X. Chen, Z. Xu, J. Wu, D. Cai,”Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse model,” Plos one, vol 8, pp 1-11, May 2013.
[13] V. Ott, G. Finlayson, H. Lehnert, B. Heitmann, M. Heinrichs, J. Born, M. Hallschmid, “Oxytocin reduces reward-driven food intake in humans,” Diabetes, vol 62, pp 3418-3425, Oct 2013.
[14] H. Yamasue, J. R. Yee, R. Hurlemann, J.K.Rilling, F.S. Chen, A.M. Lindenberg, and H. Tost, “Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction,” J Neurosci, vol 32, 14109-14117a, Oct. 2012.
[15] S. L. Aronof, K. Berkowitz, B. Shreiner, L. Want, “Glucose Metabolism and Regulation: Beyond Insulin and Glucagon,” Diabetes, vol 17(3), pp 183-190, Jul. 2004.
[16] A. F. Godoy-Matos, “The role of glucagon on type 2 diabetes at a glance, “Diabetology & Metabolic Syndrome, vol 6 (91), pp 1-5, Aug. 2014.
[17] K. Kaneko, T. Shirotani, K. Matsumoto, T. Taguchi, H. Motoshima, H. Kishikawa, M. Shichiri, “Insulin inhibits glucagon secretion by the activation of PI3 kinase in In-R1-G9 cells, "Diabetes Research and Clinical Practice, vol 44, pp 83-92, May 1999.
[18] R. S. Rita, K. Dezaki, T. Kurashina, M. Kakei, and T. Yada, “Partial blockade of Kv2.1 channel potentiates GLP-1’s insulinotropic effects in islets and reduces its dose required for improving glucose tolerance in type 2 diabetic male mice,” Endocrinology, vol 156, pp 114-123, Jan. 2015.
[19] T. Yada, N. Hamakawa, K. Yaekura, “Two distinct modes of Ca2+ signaling by Ach in rat pancreatic β-cells: concentration, glucose dependence and Ca2+ origin, “Journal of Physiology, vol 488, pp 13-24, Oct. 1995.
[20] P.E. Macdonald, Y. Z. D. Marinis, R. Ramracheya, A. Salehi, X. Ma, P.R.V. Johnson, R. Cox, L. Elasson, P. Rorsman, “A KATP channel-dependent pathway within alpha cells regulates glucagon release from both rodent and human islets of Langerhans, “Plos Biol, vol 5, 1236-1247, June.2007.
[21] E. Vieira, A. Salehi, E. Gylfe, “Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells, “Diabetologia, vol 50, pp 370-9, Feb. 2007.