The somatostatin-secreting pancreatic δ-cell in health and disease
Open accessAbstract
The somatostatin-secreting δ-cells comprise ~5% of the cells of the pancreatic islets. The δ-cells have complex morphology and might interact with many more islet cells than suggested by their low numbers. δ-Cells contain ATP-sensitive potassium channels, which open at low levels of glucose but close when glucose is elevated. This closure initiates membrane depolarization and electrical activity and increased somatostatin secretion. Factors released by neighbouring α-cells or β-cells amplify the glucose-induced effects on somatostatin secretion from δ-cells, which act locally within the islets as paracrine or autocrine inhibitors of insulin, glucagon and somatostatin secretion. The effects of somatostatin are mediated by activation of somatostatin receptors coupled to the inhibitory G protein, which culminates in suppression of the electrical activity and exocytosis in α-cells and β-cells. Somatostatin secretion is perturbed in animal models of diabetes mellitus, which might explain the loss of appropriate hypoglycaemia-induced glucagon secretion, a defect that could be mitigated by somatostatin receptor 2 antagonists. Somatostatin antagonists or agents that suppress somatostatin secretion have been proposed as an adjunct to insulin therapy. In this Review, we summarize the cell physiology of somatostatin secretion, what might go wrong in diabetes mellitus and the therapeutic potential of agents targeting somatostatin secretion or action.
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Cites
Hypothalamic Polypeptide That Inhibits the Secretion of Immunoreactive Pituitary Growth Hormone
Brazeau, P., Vale, W., Burgus, R. C., LING, N. C., Butcher, M., Rivier, J., & Guillemin, R. (1973) · Science · doi:10.1126/science.179.4068.77 · Cited by 3,536 · see citing works
Cellular energy utilization and molecular origin of standard metabolic rate in mammals
Rolfe, D. F., & Brown, G. C. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.3.731 · Cited by 2,021 · see citing works
Somatostatin and Its Receptor Family
Patel, Y. (1999) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1999.0183 · Cited by 1,648 · see citing works
Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes
Segerstolpe, Å., Palasantza, A., Eliasson, P., Andersson, E.-M., Andréasson, A.-C., Sun, X., Picelli, S., Sabirsh, A., Clausen, M., Bjursell, M. K., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.08.020 · Cited by 1,550 · see citing works
The unique cytoarchitecture of human pancreatic islets has implications for islet cell function
Cabrera, O., Berman, D. M., Kenyon, N. S., Ricordi, C., Berggren, P.-O., & Caicedo, A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510790103 · Cited by 1,312 · see citing works
Ryanodine Receptor Calcium Release Channels
Fill, M., & Copello, J. A. (2002) · Physiological Reviews · doi:10.1152/physrev.00013.2002 · Cited by 1,101 · see citing works
Lewis, K., Li, C., Perrin, M. H., Blount, A., Kunitake, K., Donaldson, C., Vaughan, J., Reyes, T. M., Gulyas, J., Fischer, W., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121165198 · Cited by 925 · see citing works
Diabetes Mellitus and the β Cell: The Last Ten Years
Ashcroft, F. M., & Rorsman, P. (2012) · Cell · doi:10.1016/j.cell.2012.02.010 · Cited by 902 · see citing works
Self-citationSurvival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study
Currie, C. J., Peters, J. R., Tynan, A., Evans, M., Heine, R. J., Bracco, O. L., Zagar, T., & Poole, C. D. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61969-3 · Cited by 874 · see citing works
Sosa‐Pineda, B., Chowdhury, K., Torres, M., Oliver, G. C., & Gruß, P. (1997) · Nature · doi:10.1038/386399a0 · Cited by 804 · see citing works
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Self-citationGerich, J. E., Langlois, M., Noacco, C., Karam, J. H., & Forsham, P. H. (1973) · Science · doi:10.1126/science.182.4108.171 · Cited by 688 · see citing works
Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium
Gribble, F. M., & Reimann, F. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105439 · Cited by 683 · see citing works
Abnormal Alpha-Cell Function in Diabetes: Response to Carbohydrate and Protein Ingestion
Müller, W. A., Faloona, G. R., Aguilar-Parada, E., & Unger, R. H. (1970) · New England Journal of Medicine · doi:10.1056/nejm197007162830301 · Cited by 626 · see citing works
Regulation of Insulin Secretion in Human Pancreatic Islets
Rorsman, P., & Braun, M. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183754 · Cited by 599 · see citing works
Self-citationOpportunities in somatostatin research: biological, chemical and therapeutic aspects
Weckbecker, G., Lewis, I., Albert, R., SCHMID, H. A., Hoyer, D., & Bruns, C. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1255 · Cited by 556 · see citing works
Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers
Chera, S., Baronnier, D., Ghila, L., Cigliola, V., Jensen, J. N., Gu, G., Furuyama, K., Thorel, F., Gribble, F. M., Reimann, F., et al. (2014) · Nature · doi:10.1038/nature13633 · Cited by 410 · see citing works
Ravier, M. A., Güldenagel, M., Charollais, A., Gjinovci, A., Caille, D., Söhl, G., Wollheim, C. B., Willecke, K., Henquin, J.-C., & Meda, P. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1798 · Cited by 360 · see citing works
Innervation Patterns of Autonomic Axons in the Human Endocrine Pancreas
Rodriguez-Diaz, R., Abdulreda, M. H., Formoso, A. L., Gans, I., Ricordi, C., Berggren, P.-O., & Caicedo, A. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.05.008 · Cited by 356 · see citing works
Prevention of Human Diabetic Ketoacidosis by Somatostatin
Gerich, J. E., Lorenzi, M., Bier, D. M., Schneider, V. B., Tsalikian, E., Karam, J. H., & Forsham, P. H. (1975) · New England Journal of Medicine · doi:10.1056/nejm197505082921901 · Cited by 353 · see citing works
DiGruccio, M. R., Mawla, A. M., Donaldson, C. J., Noguchi, G. M., Vaughan, J., Cowing-Zitron, C., van der Meulen, T., & Huising, M. O. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.04.007 · Cited by 353 · see citing works
Self-citationHauge-Evans, A. C., King, A. J., Carmignac, D., Richardson, C. C., Robinson, I. C. A. F., Low, M. J., Christie, M. R., Persaud, S. J., & Jones, P. M. (2009) · Diabetes · doi:10.2337/db08-0792 · Cited by 335 · see citing works
Blodgett, D. M., Nowosielska, A., Afik, S., Pechhold, S., Cura, A. J., Kennedy, N. J., Kim, S., Kucukural, A., Davis, R. J., Kent, S. C., et al. (2015) · Diabetes · doi:10.2337/db15-0039 · Cited by 330 · see citing works
Unbound free fatty acid levels in human serum.
Richieri, G. V., & Kleinfeld, A. M. (1995) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39899-0 · Cited by 320 · see citing works
Rodriguez‐Diaz, R., Dando, R., Jacques-Silva, M. C., Fachado, A., Molina, J., Abdulreda, M. H., Ricordi, C., Roper, S. D., Berggren, P., & Caicedo, A. (2011) · Nature Medicine · doi:10.1038/nm.2371 · Cited by 305 · see citing works
Ahrén, B., & Holst, J. J. (2001) · Diabetes · doi:10.2337/diabetes.50.5.1030 · Cited by 292 · see citing works
Urocortin3 mediates somatostatin-dependent negative feedback control of insulin secretion
van der Meulen, T., Donaldson, C. J., Cáceres, E., Hunter, A. E., Cowing-Zitron, C., Pound, L. D., Adams, M. W., Zembrzycki, A., Grove, K. L., & Huising, M. O. (2015) · Nature Medicine · doi:10.1038/nm.3872 · Cited by 256 · see citing works
Self-citationIslet Secretion in a New Experimental Model for Non-insulin-dependent Diabetes
Weir, G. C., Clore, E. T., Zmachinski, C. J., & Bonner‐Weir, S. (1981) · Diabetes · doi:10.2337/diab.30.7.590 · Cited by 248 · see citing works
Gap Junction Coupling and Calcium Waves in the Pancreatic Islet
Benninger, R. K. P., Zhang, M., Head, W. S., Satin, L. S., & Piston, D. W. (2008) · Biophysical Journal · doi:10.1529/biophysj.108.140863 · Cited by 240 · see citing works
γ-Aminobutyric Acid (GABA) Is an Autocrine Excitatory Transmitter in Human Pancreatic β-Cells
Braun, M., Ramracheya, R., Bengtsson, M., Clark, A., Walker, J. N., Johnson, P. R., & Rorsman, P. (2010) · Diabetes · doi:10.2337/db09-0797 · Cited by 239 · see citing works
Self-citationde Heer, J., Rasmussen, C. E., Coy, D. H., & Holst, J. J. (2008) · Diabetologia · doi:10.1007/s00125-008-1149-y · Cited by 238 · see citing works
The Banting Memorial Lecture 1975: Diabetes and the Alpha Cell
Unger, R. H. (1976) · Diabetes · doi:10.2337/diab.25.2.136 · Cited by 234 · see citing works
Glycemic Goals in Diabetes: Trade-off Between Glycemic Control and Iatrogenic Hypoglycemia
Cryer, P. E. (2014) · Diabetes · doi:10.2337/db14-0059 · Cited by 233 · see citing works
A 3D map of the islet routes throughout the healthy human pancreas
Ionescu-Tirgoviste, C., Gagniuc, P. A., Gagniuc, E., Mardare, L., Popescu, I., Dima, S., & Militaru, M. (2015) · Scientific Reports · doi:10.1038/srep14634 · Cited by 230 · see citing works
Glucagon: Role in the Hyperglycemia of Diabetes Mellitus
Dobbs, R., Sakurai, H., Sasaki, H., Faloona, G., Valverde, I., Baetens, D., Orci, L., & Unger, R. (1975) · Science · doi:10.1126/science.1089999 · Cited by 229 · see citing works
Zhang, Q., Ramracheya, R., Lahmann, C., Tarasov, A., Bengtsson, M., Braha, O., Braun, M., Brereton, M., Collins, S., Galvanovskis, J., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.10.014 · Cited by 225 · see citing works
Self-citationAdriaenssens, A. E., Svendsen, B., Lam, B. Y. H., Yeo, G. S. H., Holst, J. J., Reimann, F., & Gribble, F. M. (2016) · Diabetologia · doi:10.1007/s00125-016-4033-1 · Cited by 223 · see citing works
Glucose inhibits glucagon secretion by a direct effect on mouse pancreatic alpha cells
Vieira, E., Salehi, A., & Gylfe, E. (2007) · Diabetologia · doi:10.1007/s00125-006-0511-1 · Cited by 218 · see citing works
Brereton, M. F., Vergari, E., Zhang, Q., & Clark, A. (2015) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155415583535 · Cited by 206 · see citing works
The order of islet microvascular cellular perfusion is B----A----D in the perfused rat pancreas.
Samols, E., Stagner, J. I., Ewart, R. B. L., & Marks, V. (1988) · Journal of Clinical Investigation · doi:10.1172/jci113593 · Cited by 204 · see citing works
Hyperglucagonemia and Its Suppression
Raskin, P., & Unger, R. H. (1978) · New England Journal of Medicine · doi:10.1056/nejm197808312990901 · Cited by 197 · see citing works
Nadal, Á., Quesada, I., & Soria, B. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.0085z.x · Cited by 196 · see citing works
Renström, E., Ding, W.-G., Bokvist, K., & Rorsman, P. (1996) · Neuron · doi:10.1016/s0896-6273(00)80183-x · Cited by 186 · see citing works
Self-citationDistribution of HbA1c Levels For Children and Young Adults in the U.S.
Saaddine, J. B., Fagot-Campagna, A., Rolka, D., Narayan, K. M. V., Geiss, L., Eberhardt, M., & Flegal, K. M. (2002) · Diabetes Care · doi:10.2337/diacare.25.8.1326 · Cited by 177 · see citing works
Regulation of glucagon secretion by glucose: paracrine, intrinsic or both?
Walker, J. N., Ramracheya, R. D., Zhang, Q., Johnson, P., Braun, M., & Rorsman, P. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01450.x · Cited by 174 · see citing works
Self-citationSSTR2 is the functionally dominant somatostatin receptor in human pancreatic β- and α-cells
Kailey, B., van de Bunt, M., Cheley, S., Johnson, P. R., MacDonald, P. E., Gloyn, A. L., Rorsman, P., & Braun, M. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00207.2012 · Cited by 164 · see citing works
Self-citationIpp, E., DOBBS, R. E., Arimura, A., Vale, W. W., Harris, V. K., & Unger, R. H. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108829 · Cited by 163 · see citing works
δ‐cells and β‐cells are electrically coupled and regulate α‐cell activity via somatostatin
Briant, L. J. B., Reinbothe, T. M., Spiliotis, I., Miranda, C., Rodriguez, B., & Rorsman, P. (2018) · The Journal of Physiology · doi:10.1113/jp274581 · Cited by 155 · see citing works
Self-citationPatch‐clamp characterisation of somatostatin‐secreting δ‐cells in intact mouse pancreatic islets
Göpel, S., Kanno, T., Barg, S., & Rorsman, P. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00497.x · Cited by 143 · see citing works
Self-citationStone, V. M., Dhayal, S., Brocklehurst, K. J., Lenaghan, C., Winzell, M. S., Hammar, M., Xu, X., Smith, D. M., & Morgan, N. G. (2014) · Diabetologia · doi:10.1007/s00125-014-3213-0 · Cited by 128 · see citing works
Gromada, J., Høy, M., Buschard, K., Salehi, A., & Rorsman, P. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.00519.x · Cited by 120 · see citing works
Self-citationNørgaard, A., Kjeldsen, K. P., & Clausen, T. (1981) · Nature · doi:10.1038/293739a0 · Cited by 115 · see citing works
R-type Ca2+-channel-evoked CICR regulates glucose-induced somatostatin secretion
Zhang, Q., Bengtsson, M., Partridge, C., Salehi, A., Braun, M., Cox, R., Eliasson, L., Johnson, P. R., Renström, E., Schneider, T., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1563 · Cited by 110 · see citing works
Self-citationPancreatic immunoreactive somatostatin release.
Patton, G. S., Ipp, E., DOBBS, R. E., et al. (1977) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.74.5.2140 · Cited by 105 · see citing works
Braun, M., Ramracheya, R., Amisten, S., Bengtsson, M., Moritoh, Y., Zhang, Q., Johnson, P. R. V., & Rorsman, P. (2009) · Diabetologia · doi:10.1007/s00125-009-1382-z · Cited by 104 · see citing works
Self-citationThe role of somatostatin in GLP-1-induced inhibition of glucagon secretion in mice
Orgaard, A., & Holst, J. (2017) · Diabetologia · doi:10.1007/s00125-017-4315-2 · Cited by 102 · see citing works
Quesada, I., Nadal, A., & Soria, B. (1999) · Diabetes · doi:10.2337/diabetes.48.12.2390 · Cited by 99 · see citing works
Glucose regulation of glucagon secretion
Gylfe, E., & Gilon, P. (2013) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2013.11.019 · Cited by 98 · see citing works
Olofsson, C., Salehi, A., Göpel, S., Holm, C., & Rorsman, P. (2004) · Diabetes · doi:10.2337/diabetes.53.11.2836 · Cited by 95 · see citing works
Self-citationAttenuation of Counterregulatory Responses to Recurrent Hypoglycemia by Active Thalamic Inhibition
Arbelaez, A. M., Powers, W. J., Videen, T. O., Price, J. L., & Cryer, P. E. (2008) · Diabetes · doi:10.2337/db07-1329 · Cited by 92 · see citing works
Nicolas, G. P., Beykan, S., Bouterfa, H., Kaufmann, J., Bauman, A., Laßmann, M., Reubi, J. C., Rivier, J., Maëcke, H. R., Fani, M., et al. (2017) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.199737 · Cited by 92 · see citing works
Pharmacology and physiology of gastrointestinal enteroendocrine cells
Mace, O. J., Tehan, B. G., & Marshall, F. H. (2015) · Pharmacology Research & Perspectives · doi:10.1002/prp2.155 · Cited by 91 · see citing works
Zhang, Q., Chibalina, M. V., Bengtsson, M., Groschner, L. N., Ramracheya, R., Rorsman, N. J. G., Leiss, V., Nassar, M. A., Welling, A., Gribble, F. M., et al. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.274209 · Cited by 90 · see citing works
Self-citationRorsman, P., Ramracheya, R. D., Rorsman, N. J. G., & Zhang, Q. (2014) · Diabetologia · doi:10.1007/s00125-014-3279-8 · Cited by 89 · see citing works
Self-citationAdriaenssens, A. E., Lam, B., Billing, L., Skeffington, K. L., Sewing, S., Reimann, F. M., & Gribble, F. M. (2015) · Endocrinology · doi:10.1210/en.2015-1301 · Cited by 88 · see citing works
Olofsson, C. S., Salehi, A., Holm, C., & Rorsman, P. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.066258 · Cited by 88 · see citing works
Self-citationIlluminating somatostatin analog action at neuroendocrine tumor receptors
Reubi, J. C., & Schönbrunn, A. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.10.001 · Cited by 88 · see citing works
Inhibition of thein VitroSecretion of Insulin by an Extract of Pancreaticα1Cells
Hellman, B., & Lernmark, Å. (1969) · Endocrinology · doi:10.1210/endo-84-6-1484 · Cited by 87 · see citing works
Panten, U., Kriegstein, E. V., Poser, W., Schönborn, J., & Hasselblatt, A. (1972) · FEBS Letters · doi:10.1016/0014-5793(72)80801-9 · Cited by 86 · see citing works
Cell coupling in mouse pancreatic β-cells measured in intact islets of Langerhans
Zhang, Q., Galvanovskis, J., Abdulkader, F., Partridge, C. J., Göpel, S. O., Eliasson, L., & Rorsman, P. (2008) · Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences · doi:10.1098/rsta.2008.0110 · Cited by 80 · see citing works
Self-citationHypokalemia in Acute Medical Patients: Risk Factors and Prognosis
Kildegaard, H., Brabrand, M., Vinholt, P. J., Hallas, J., & Lassen, A. T. (2014) · The American Journal of Medicine · doi:10.1016/j.amjmed.2014.07.022 · Cited by 77 · see citing works
Yue, J. T. Y., Burdett, E., Coy, D. H., Giacca, A., Efendic, S., & Vranic, M. (2012) · Diabetes · doi:10.2337/db11-0690 · Cited by 75 · see citing works
Hellman, B. (1959) · Nature · doi:10.1038/1841498a0 · Cited by 74 · see citing works
Immunoreactive somatostatin levels in plasma of normal and alloxan diabetic dogs
SCHUSDZIARRA, V., DOBBS, R. E., Harris, V., et al. (1977) · FEBS Letters · doi:10.1016/0014-5793(77)80930-7 · Cited by 70 · see citing works
Gα i/o -coupled receptor signaling restricts pancreatic β-cell expansion
Berger, M., Scheel, D. W., Macias, H., Miyatsuka, T., Kim, H., Hoang, P. T., Ku, G. M., Honig, G., Liou, A., Tang, Y., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319378112 · Cited by 68 · see citing works
Efendić, S., Enzmann, F., Nylén, A., Uvnäs‐Wallensten, K., & Luft, R. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.11.5901 · Cited by 67 · see citing works
Submembrane ATP and Ca2+kinetics in α-cells: unexpected signaling for glucagon secretion
Li, J., Yu, Q., Ahooghalandari, P., Gribble, F. M., Reimann, F. M., Tengholm, A., & Gylfe, E. (2015) · The FASEB Journal · doi:10.1096/fj.14-265918 · Cited by 67 · see citing works
Contribution of the pancreas to circulating somatostatin-like immunoreactivity in the normal dog.
Taborsky, G. J., & Ensinck, J. W. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111194 · Cited by 67 · see citing works
Gerich, J. E., Schultz, T. A., Lewis, S. B., et al. (1977) · Diabetologia · doi:10.1007/bf01234510 · Cited by 66 · see citing works
Karimian, N., Qin, T., Liang, T., Osundiji, M., Huang, Y., Teich, T., Riddell, M. C., Cattral, M. S., Coy, D. H., Vranic, M., et al. (2013) · Diabetes · doi:10.2337/db13-0164 · Cited by 66 · see citing works
The somatostatin receptor in human pancreatic β-cells.
Braun, M. (2014) · Vitamins and hormones · doi:10.1016/b978-0-12-800174-5.00007-7 · Cited by 60 · see citing works
Functional identification of islet cell types by electrophysiological fingerprinting
Briant, L. J. B., Zhang, Q., Vergari, E., Kellard, J. A., Rodriguez, B., Ashcroft, F. M., & Rorsman, P. (2017) · Journal of The Royal Society Interface · doi:10.1098/rsif.2016.0999 · Cited by 59 · see citing works
Self-citationAbdel‐Halim, S. M., Guenifi, A., Efendić, S., & Östenson, C. (1993) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1993.tb09551.x · Cited by 58 · see citing works
Baskin, D. G. (2015) · Journal of Histochemistry & Cytochemistry · doi:10.1369/0022155415589119 · Cited by 53 · see citing works
Glucose stimulation of somatostatin-producing islet cells involves oscillatory Ca2+ signaling
Berts, A., Ball, A., Dryselius, G., Gylfe, E., & Hellman, B. (1996) · Endocrinology · doi:10.1210/endo.137.2.8593819 · Cited by 53 · see citing works
Sorenson, R. L., Elde, R. P., & Seybold, V. S. (1979) · Diabetes · doi:10.2337/diab.28.10.899 · Cited by 49 · see citing works
Yue, J. T. Y., Riddell, M. C., Burdett, E., Coy, D. H., Efendic, S., & Vranic, M. (2013) · Diabetes · doi:10.2337/db12-1523 · Cited by 45 · see citing works
Hypoglycemia-Associated Autonomic Failure in Diabetes: Maladaptive, Adaptive, or Both?
Cryer, P. E. (2015) · Diabetes · doi:10.2337/db15-0331 · Cited by 43 · see citing works
Glucose and glucagon stimulate the secretion of somatostatin from the perfused canine pancreas
Weir, G. C., Samols, E., Day, J. A., & Patel, Y. (1978) · Metabolism · doi:10.1016/0026-0495(78)90047-1 · Cited by 39 · see citing works
Streptozotocin diabetes: A glucoreceptor dysfunction affecting D cells as well as B and A cells
Hermansen, K., �rskov, H., & Christensen, S. E. (1979) · Diabetologia · doi:10.1007/bf01236274 · Cited by 38 · see citing works
Vivot, K., Moullé, V. S. F., Zarrouki, B., Tremblay, C. C., Mancini, A. D., Maachi, H., Ghislain, J. J., & Poitout, V. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.08.010 · Cited by 37 · see citing works
QT prolongation caused by insulin-induced hypoglycaemia – An interventional study in 119 individuals
Kacheva, S., Karges, B., Göller, K., Marx, N., Mischke, K., & Karges, W. (2016) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2016.11.021 · Cited by 37 · see citing works
Involvement of MAP kinase and c-fos signaling in the inhibition of cell growth by somatostatin
Yoshitomi, H., Fujii, Y., Miyazaki, M., et al. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.272.5.e769 · Cited by 36 · see citing works
Honey, R. N., Fallon, M. B., & Weir, G. C. (1980) · Metabolism · doi:10.1016/0026-0495(80)90152-3 · Cited by 36 · see citing works
Gerber, P. P. G., Trimble, E. R., Wollheim, C. B., et al. (1981) · Diabetes · doi:10.2337/diab.30.1.40 · Cited by 35 · see citing works
Gerber, P. P. G., Trimble, E. R., Wollheim, C. B., et al. (1981) · Endocrinology · doi:10.1210/endo-109-1-279 · Cited by 34 · see citing works
Delta cell secretory responses to insulin secretagogues are not mediated indirectly by insulin
Hauge-Evans, A. C., Anderson, R. L., Persaud, S. J., & Jones, P. M. (2012) · Diabetologia · doi:10.1007/s00125-012-2546-9 · Cited by 33 · see citing works
Sako, Y., Wasada, T., Umeda, F., et al. (1986) · Metabolism · doi:10.1016/0026-0495(86)90059-4 · Cited by 25 · see citing works
Evidence for an inhibitor of insulin release in the pancreatic islets
Hellman, B., & Lernmark, Å. (1969) · Diabetologia · doi:10.1007/bf01212214 · Cited by 24 · see citing works
D’Alessio, D. A., & Ensinck, J. W. (1990) · Diabetes · doi:10.2337/diab.39.10.1198 · Cited by 24 · see citing works
Conlon, J. M., McCulloch, A. J., & Alberti, K. G. M. M. (1983) · Diabetes · doi:10.2337/diab.32.8.723 · Cited by 24 · see citing works
A Strong Stomach for Somatostatin
Mani, B. K., & Zigman, J. M. (2015) · Endocrinology · doi:10.1210/en.2015-1756 · Cited by 20 · see citing works
Caduff, A., Lutz, H. U., Heinemann, L., Benedetto, G. D., Talary, M. S., & Theander, S. S. (2011) · Diabetologia · doi:10.1007/s00125-011-2210-9 · Cited by 20 · see citing works
Hermansen, K. (1981) · Diabetes · doi:10.2337/diab.30.3.203 · Cited by 19 · see citing works
Characterization of somatostatin release from the pancreas: the role of potassium
Hermansen, K., Christensen, S. E., & Ørskov, H. (1979) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365517909108162 · Cited by 16 · see citing works
Tolbutamide, glucose, calcium, and somatostatin secretion
Hermansen, K. (1982) · European Journal of Endocrinology · doi:10.1530/acta.0.0990086 · Cited by 12 · see citing works
Can somatostatin antagonism prevent hypoglycaemia during exercise in type 1 diabetes?
Taleb, N., & RABASA-LHORET, R. P. R. (2016) · Diabetologia · doi:10.1007/s00125-016-3978-4 · Cited by 12 · see citing works
The Significance of the Na+/K+Pump for Somatostatin Release
Hermansen, K., Christensen, S., & Ørskov, H. (1980) · Hormone and Metabolic Research · doi:10.1055/s-2007-996187 · Cited by 7 · see citing works
Guillemin, R. (1992) · Metabolism · doi:10.1016/0026-0495(92)90022-3 · Cited by 7 · see citing works
Martı́nez, V., & Taché, Y. (2004) · Encyclopedia of Gastroenterology · doi:10.1016/b0-12-386860-2/00657-2 · Cited by 7 · see citing works
Stimulation of somatostatin secretion by 3-O-methylglucose in the perfused dog pancreas
Hermansen, K., LINDSKOG, S., & Åhrén, B. (1996) · International Journal of Pancreatology · doi:10.1007/bf02825508 · Cited by 3 · see citing works
2 CATIONIC AMINO-ACID TRANSPORTERS EXPRESSED IN PANCREATIC BETA-CELLS
Ashcroft, F. M., Coles, B., Gummerson, N. W., et al. (1995) · The Journal of Physiology · Cited by 2 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- [3]Frayn KN Metabolic regulation: a human perspective 384 Oxford Wiley-Blackwell 2010
- [37]Adriaenssens A A Transcriptome-Led Exploration of Molecular Mechanisms Regulating Somatostatin-Producing D-Cells in the Gastric Epithelium Endocrinology 156 3924 36 2015 26241122 PMC4606756
- [46]Rorsman P Ashcroft FM Pancreatic beta-Cell Electrical Activity and Insulin Secretion: Of Mice and Men Physiol Rev 98 117 214 2018 29212789 PMC5866358
- [60]Briant LJB delta-cells and beta-cells are electrically coupled and regulate alpha-cell activity via somatostatin J Physiol 2017 PMC5767697 28975620
- [61]Zhang Q Na+ current properties in islet alpha- and beta-cells reflect cell-specific Scn3a and Scn9a expression J Physiol 592 4677 96 2014 25172946 PMC4253470
- [74]Rodriguez-Diaz R Innervation Patterns of Autonomic Axons in the Human Endocrine Pancreas Cell Metabolism 14 45 54 2011 21723503 PMC3135265
- [88]Orgaard A Holst JJ The role of somatostatin in GLP-1-induced inhibition of glucagon secretion in mice Diabetologia 60 1731 1739 2017 28551699 PMC5552842
- [89]Adriaenssens AE Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets Diabetologia 59 2156 2165 2016 27390011 PMC5016554
- [100]Dalessio DA Ensinck JW Fasting and Postprandial Concentrations of Somatostatin-28 and Somatostatin-14 in Type-Ii Diabetes in Men Diabetes 39 1198 1202 1990 1976558
Cited by
Sorted by citations
Insulin inhibits glucagon release by SGLT2-induced stimulation of somatostatin secretion
Vergari, E., Knudsen, J. G., Ramracheya, R., Salehi, A., Zhang, Q., Adam, J., Asterholm, I. W., Benrick, A., Briant, L. J. B., Chibalina, M. V., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08193-8 · Cited by 152 · see citing works
Self-citation100 years of glucagon and 100 more
Wewer Albrechtsen, N. J., Holst, J. J., Cherrington, A. D., Finan, B., Gluud, L. L., Dean, E. D., Campbell, J. E., Bloom, S. R., Tan, T. M.-M., Knop, F. K., et al. (2023) · Diabetologia · doi:10.1007/s00125-023-05947-y · Cited by 117 · see citing works
First-phase insulin secretion: can its evaluation direct therapeutic approaches?
Di Giuseppe, G., Ciccarelli, G., Soldovieri, L., Capece, U., Cefalo, C. M. A., Moffa, S., Nista, E. C., Brunetti, M., Cinti, F., Gasbarrini, A., et al. (2023) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2023.02.001 · Cited by 46 · see citing works
Somatostatin secretion by Na+-dependent Ca2+-induced Ca2+ release in pancreatic delta cells
Vergari, E., Denwood, G., Salehi, A., Zhang, Q., Adam, J., Alrifaiy, A., Wernstedt Asterholm, I., Benrick, A., Chibalina, M. V., Eliasson, L., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0158-0 · Cited by 43 · see citing works
Self-citationCharacterization of stem-cell-derived islets during differentiation and after implantation
Cuesta-Gomez, N., Verhoeff, K., Jasra, I. T., Pawlick, R., Dadheech, N., & Shapiro, A. M. J. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111238 · Cited by 41 · see citing works
GLP1R and GIPR expression and signaling in pancreatic alpha cells, beta cells and delta cells
Shilleh, A. H., Viloria, K., Broichhagen, J., Campbell, J. E., & Hodson, D. J. (2024) · Peptides · doi:10.1016/j.peptides.2024.171179 · Cited by 39 · see citing works
Hill, T. G., Gao, R., Benrick, A., Kothegala, L., Rorsman, N., Santos, C., Acreman, S., Briant, L. J., Dou, H., Gandasi, N. R., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01139-z · Cited by 30 · see citing works
“Somatostatin-secreting δ-cells are equipped with K ATP channels that are identical to those in β-cells 31 .”
Self-citationHoffman, E. G., D’Souza, N. C., Liggins, R. T., & Riddell, M. C. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1295639 · Cited by 13 · see citing works
Heterogeneous alpha-cell population modeling of glucose-induced inhibition of electrical activity
Montefusco, F., Cortese, G., & Pedersen, M. G. (2020) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2019.110036 · Cited by 13 · see citing works
- Authors
- Rorsman, P., & Huising, M. O.
- Affiliations
- Churchill Hospital (GB)
- University of California, Davis (US)
- Corresponding author
- Rorsman, Patrik
- Venue
- Nature Reviews Endocrinology
- Published
- 2018-05-17
- Volume
- 14
- Issue
- 7
- Pages
- 404-414
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- PMC
- PMC5997567
- OpenAlex
- W2803302591
- Cited by
- 259
- References
- 112
- Citations by year
- 2026: 24 · 2025: 36 · 2024: 38 · 2023: 36 · 2022: 34 · 2021: 32 · 2020: 31 · 2019: 21 · 2018: 7
- FWCI
- 5.05
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- Wellcome Trust (095531/Z/11/Z)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK110276)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- pancreatic delta cells, somatostatin secretion, pancreatic islets, ATP-sensitive potassium channels, somatostatin receptors, G protein signaling, glucagon secretion, hypoglycemia, diabetes mellitus
- MeSH terms
- Animals, Diabetes Mellitus, Female, Glucagon, Humans, Hypoglycemia, Male, Prognosis, Reference Values, Somatostatin, Biomarkers, Case-Control Studies, Treatment Outcome, Receptors, Somatostatin, Somatostatin-Secreting Cells
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