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Erschienen in: Current Diabetes Reports 11/2018

01.11.2018 | Pathogenesis of Type 1 Diabetes (A Pugliese and SJ Richardson, Section Editors)

The Role of Accessory Cells in Islet Homeostasis

verfasst von: Shiue-Cheng Tang, Claire F. Jessup, Martha Campbell-Thompson

Erschienen in: Current Diabetes Reports | Ausgabe 11/2018

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Abstract

Purposes of Review

Scattered throughout the pancreas, the endocrine islets rely on neurovascular support for signal relay to regulate hormone secretion and for maintaining tissue homeostasis. The islet accessory cells (or components) of neurovascular tissues include the endothelial cells, pericytes, smooth muscle cells, neurons (nerve fibers), and glia. Research results derived from experimental diabetes and islet transplantation indicate that the accessory cells are reactive in islet injury and can affect islet function and homeostasis in situ or in an ectopic environment.

Recent Findings

Recent advances in cell labeling and tissue imaging have enabled investigation of islet accessory cells to gain insights into their network structures, functions, and remodeling in disease.

Summary

It has become clear that in diabetes, the islet neurovascular tissues are not just bystanders damaged in neuropathy and vascular complications; rather, they participate in islet remodeling in response to changes in the microenvironment. Because of the fundamental differences between humans and animal models in neuroinsular cytoarchitecture and cell proliferation, examination of islet accessory cells in clinical specimens and donor pancreases warrants further attention.
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Literatur
1.
Zurück zum Zitat Meyer HH, Vetterlein F, Schmidt G, Hasselblatt A. Measurement of blood flow in pancreatic islets of the rat: effect of isoproterenol and norepinephrine. Am J Phys. 1982;242(5):E298–304. Meyer HH, Vetterlein F, Schmidt G, Hasselblatt A. Measurement of blood flow in pancreatic islets of the rat: effect of isoproterenol and norepinephrine. Am J Phys. 1982;242(5):E298–304.
2.
Zurück zum Zitat Lifson N, Lassa CV, Dixit PK. Relation between blood flow and morphology in islet organ of rat pancreas. Am J Phys. 1985;249(1 Pt 1):E43–8. Lifson N, Lassa CV, Dixit PK. Relation between blood flow and morphology in islet organ of rat pancreas. Am J Phys. 1985;249(1 Pt 1):E43–8.
3.
Zurück zum Zitat Nyqvist D, Speier S, Rodriguez-Diaz R, Molano RD, Lipovsek S, Rupnik M, et al. Donor islet endothelial cells in pancreatic islet revascularization. Diabetes. 2011;60(10):2571–7.CrossRef Nyqvist D, Speier S, Rodriguez-Diaz R, Molano RD, Lipovsek S, Rupnik M, et al. Donor islet endothelial cells in pancreatic islet revascularization. Diabetes. 2011;60(10):2571–7.CrossRef
4.
Zurück zum Zitat Jansson L, Barbu A, Bodin B, Drott CJ, Espes D, Gao X, et al. Pancreatic islet blood flow and its measurement. Ups J Med Sci. 2016;121(2):81–95.CrossRef Jansson L, Barbu A, Bodin B, Drott CJ, Espes D, Gao X, et al. Pancreatic islet blood flow and its measurement. Ups J Med Sci. 2016;121(2):81–95.CrossRef
5.
Zurück zum Zitat Iwashita N, Uchida T, Choi JB, Azuma K, Ogihara T, Ferrara N, et al. Impaired insulin secretion in vivo but enhanced insulin secretion from isolated islets in pancreatic beta cell-specific vascular endothelial growth factor-A knock-out mice. Diabetologia. 2007;50(2):380–9.CrossRef Iwashita N, Uchida T, Choi JB, Azuma K, Ogihara T, Ferrara N, et al. Impaired insulin secretion in vivo but enhanced insulin secretion from isolated islets in pancreatic beta cell-specific vascular endothelial growth factor-A knock-out mice. Diabetologia. 2007;50(2):380–9.CrossRef
6.
Zurück zum Zitat Nikolova G, Jabs N, Konstantinova I, Domogatskaya A, Tryggvason K, Sorokin L, et al. The vascular basement membrane: a niche for insulin gene expression and Beta cell proliferation. Dev Cell. 2006;10(3):397–405.CrossRef Nikolova G, Jabs N, Konstantinova I, Domogatskaya A, Tryggvason K, Sorokin L, et al. The vascular basement membrane: a niche for insulin gene expression and Beta cell proliferation. Dev Cell. 2006;10(3):397–405.CrossRef
7.
Zurück zum Zitat Sordi V, Ferri A, Ceserani V, Ciusani E, Dugnani E, Pellegrini S, et al. Establishment, characterization and long-term culture of human endocrine pancreas-derived microvascular endothelial cells. Cytotherapy. 2017;19(1):141–52.CrossRef Sordi V, Ferri A, Ceserani V, Ciusani E, Dugnani E, Pellegrini S, et al. Establishment, characterization and long-term culture of human endocrine pancreas-derived microvascular endothelial cells. Cytotherapy. 2017;19(1):141–52.CrossRef
9.
Zurück zum Zitat Zanone MM, Favaro E, Doublier S, Lozanoska-Ochser B, Deregibus MC, Greening J, et al. Expression of nephrin by human pancreatic islet endothelial cells. Diabetologia. 2005;48(9):1789–97.CrossRef Zanone MM, Favaro E, Doublier S, Lozanoska-Ochser B, Deregibus MC, Greening J, et al. Expression of nephrin by human pancreatic islet endothelial cells. Diabetologia. 2005;48(9):1789–97.CrossRef
10.
Zurück zum Zitat Villarreal R, Mitrofanova A, Maiguel D, Morales X, Jeon J, Grahammer F, et al. Nephrin Contributes to Insulin Secretion and Affects Mammalian Target of Rapamycin Signaling Independently of Insulin Receptor. J Am Soc Nephrol. 2016;27(4):1029–41.CrossRef Villarreal R, Mitrofanova A, Maiguel D, Morales X, Jeon J, Grahammer F, et al. Nephrin Contributes to Insulin Secretion and Affects Mammalian Target of Rapamycin Signaling Independently of Insulin Receptor. J Am Soc Nephrol. 2016;27(4):1029–41.CrossRef
11.
Zurück zum Zitat Lou J, Triponez F, Oberholzer J, Wang H, Yu D, Buhler L, et al. Expression of alpha-1 proteinase inhibitor in human islet microvascular endothelial cells. Diabetes. 1999;48(9):1773–8.CrossRef Lou J, Triponez F, Oberholzer J, Wang H, Yu D, Buhler L, et al. Expression of alpha-1 proteinase inhibitor in human islet microvascular endothelial cells. Diabetes. 1999;48(9):1773–8.CrossRef
12.
Zurück zum Zitat Kang S, Park HS, Jo A, Hong SH, Lee HN, Lee YY, et al. Endothelial progenitor cell cotransplantation enhances islet engraftment by rapid revascularization. Diabetes. 2012;61(4):866–76.CrossRef Kang S, Park HS, Jo A, Hong SH, Lee HN, Lee YY, et al. Endothelial progenitor cell cotransplantation enhances islet engraftment by rapid revascularization. Diabetes. 2012;61(4):866–76.CrossRef
13.
Zurück zum Zitat Oh BJ, Oh SH, Jin SM, Suh S, Bae JC, Park CG, et al. Co-transplantation of bone marrow-derived endothelial progenitor cells improves revascularization and organization in islet grafts. Am J Transplant. 2013;13(6):1429–40.CrossRef Oh BJ, Oh SH, Jin SM, Suh S, Bae JC, Park CG, et al. Co-transplantation of bone marrow-derived endothelial progenitor cells improves revascularization and organization in islet grafts. Am J Transplant. 2013;13(6):1429–40.CrossRef
14.
Zurück zum Zitat Penko D, Rojas-Canales D, Mohanasundaram D, Peiris HS, Sun WY, Drogemuller CJ, et al. Endothelial progenitor cells enhance islet engraftment, influence beta-cell function, and modulate islet connexin 36 expression. Cell Transplant. 2015;24(1):37–48.CrossRef Penko D, Rojas-Canales D, Mohanasundaram D, Peiris HS, Sun WY, Drogemuller CJ, et al. Endothelial progenitor cells enhance islet engraftment, influence beta-cell function, and modulate islet connexin 36 expression. Cell Transplant. 2015;24(1):37–48.CrossRef
15.
Zurück zum Zitat Linn T, Schneider K, Hammes HP, Preissner KT, Brandhorst H, Morgenstern E, et al. Angiogenic capacity of endothelial cells in islets of Langerhans. FASEB J. 2003;17(8):881–3.CrossRef Linn T, Schneider K, Hammes HP, Preissner KT, Brandhorst H, Morgenstern E, et al. Angiogenic capacity of endothelial cells in islets of Langerhans. FASEB J. 2003;17(8):881–3.CrossRef
16.
Zurück zum Zitat Nyqvist D, Kohler M, Wahlstedt H, Berggren PO. Donor islet endothelial cells participate in formation of functional vessels within pancreatic islet grafts. Diabetes. 2005;54(8):2287–93.CrossRef Nyqvist D, Kohler M, Wahlstedt H, Berggren PO. Donor islet endothelial cells participate in formation of functional vessels within pancreatic islet grafts. Diabetes. 2005;54(8):2287–93.CrossRef
17.
Zurück zum Zitat Aamodt KI, Powers AC. Signals in the pancreatic islet microenvironment influence beta-cell proliferation. Diabetes Obes Metab. 2017;19(Suppl 1):124–36.CrossRef Aamodt KI, Powers AC. Signals in the pancreatic islet microenvironment influence beta-cell proliferation. Diabetes Obes Metab. 2017;19(Suppl 1):124–36.CrossRef
18.
Zurück zum Zitat Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood vessels. Science. 2001;294(5542):564–7.CrossRef Lammert E, Cleaver O, Melton D. Induction of pancreatic differentiation by signals from blood vessels. Science. 2001;294(5542):564–7.CrossRef
19.
Zurück zum Zitat Yoshitomi H, Zaret KS. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development. 2004;131(4):807–17.CrossRef Yoshitomi H, Zaret KS. Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1a. Development. 2004;131(4):807–17.CrossRef
20.
Zurück zum Zitat Brissova M, Shostak A, Shiota M, Wiebe PO, Poffenberger G, Kantz J, et al. Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization, revascularization, and function. Diabetes. 2006;55(11):2974–85.CrossRef Brissova M, Shostak A, Shiota M, Wiebe PO, Poffenberger G, Kantz J, et al. Pancreatic islet production of vascular endothelial growth factor--a is essential for islet vascularization, revascularization, and function. Diabetes. 2006;55(11):2974–85.CrossRef
21.
Zurück zum Zitat Reinert RB, Brissova M, Shostak A, Pan FC, Poffenberger G, Cai Q, et al. Vascular endothelial growth factor-a and islet vascularization are necessary in developing, but not adult, pancreatic islets. Diabetes. 2013;62(12):4154–64.CrossRef Reinert RB, Brissova M, Shostak A, Pan FC, Poffenberger G, Cai Q, et al. Vascular endothelial growth factor-a and islet vascularization are necessary in developing, but not adult, pancreatic islets. Diabetes. 2013;62(12):4154–64.CrossRef
22.
Zurück zum Zitat Kuboki K, Jiang ZY, Takahara N, Ha SW, Igarashi M, Yamauchi T, et al. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo : a specific vascular action of insulin. Circulation. 2000;101(6):676–81.CrossRef Kuboki K, Jiang ZY, Takahara N, Ha SW, Igarashi M, Yamauchi T, et al. Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo : a specific vascular action of insulin. Circulation. 2000;101(6):676–81.CrossRef
23.
Zurück zum Zitat Carlsson PO, Andersson A, Jansson L. Influence of age, hyperglycemia, leptin, and NPY on islet blood flow in obese-hyperglycemic mice. Am J Phys. 1998;275(4 Pt 1):E594–601. Carlsson PO, Andersson A, Jansson L. Influence of age, hyperglycemia, leptin, and NPY on islet blood flow in obese-hyperglycemic mice. Am J Phys. 1998;275(4 Pt 1):E594–601.
24.
Zurück zum Zitat Dai C, Brissova M, Reinert RB, Nyman L, Liu EH, Thompson C, et al. Pancreatic islet vasculature adapts to insulin resistance through dilation and not angiogenesis. Diabetes. 2013;62(12):4144–53.CrossRef Dai C, Brissova M, Reinert RB, Nyman L, Liu EH, Thompson C, et al. Pancreatic islet vasculature adapts to insulin resistance through dilation and not angiogenesis. Diabetes. 2013;62(12):4144–53.CrossRef
25.
Zurück zum Zitat • Almaca J, Weitz J, Rodriguez-Diaz R, Pereira E, Caicedo A. The Pericyte of the Pancreatic Islet Regulates Capillary Diameter and Local Blood Flow. Cell Metab. 2018;27(3):630–644. Demonstrates the islet neurovascular integration. CrossRef • Almaca J, Weitz J, Rodriguez-Diaz R, Pereira E, Caicedo A. The Pericyte of the Pancreatic Islet Regulates Capillary Diameter and Local Blood Flow. Cell Metab. 2018;27(3):630–644. Demonstrates the islet neurovascular integration. CrossRef
26.
Zurück zum Zitat Gregersen S, Thomsen JL, Brock B, Hermansen K. Endothelin-1 stimulates insulin secretion by direct action on the islets of Langerhans in mice. Diabetologia. 1996;39(9):1030–5.CrossRef Gregersen S, Thomsen JL, Brock B, Hermansen K. Endothelin-1 stimulates insulin secretion by direct action on the islets of Langerhans in mice. Diabetologia. 1996;39(9):1030–5.CrossRef
27.
Zurück zum Zitat Garcia-Ocana A, Takane KK, Reddy VT, Lopez-Talavera JC, Vasavada RC, Stewart AF. Adenovirus-mediated hepatocyte growth factor expression in mouse islets improves pancreatic islet transplant performance and reduces beta cell death. J Biol Chem. 2003;278(1):343–51.CrossRef Garcia-Ocana A, Takane KK, Reddy VT, Lopez-Talavera JC, Vasavada RC, Stewart AF. Adenovirus-mediated hepatocyte growth factor expression in mouse islets improves pancreatic islet transplant performance and reduces beta cell death. J Biol Chem. 2003;278(1):343–51.CrossRef
28.
Zurück zum Zitat Olerud J, Mokhtari D, Johansson M, Christoffersson G, Lawler J, Welsh N, et al. Thrombospondin-1: an islet endothelial cell signal of importance for beta-cell function. Diabetes. 2011;60(7):1946–54.CrossRef Olerud J, Mokhtari D, Johansson M, Christoffersson G, Lawler J, Welsh N, et al. Thrombospondin-1: an islet endothelial cell signal of importance for beta-cell function. Diabetes. 2011;60(7):1946–54.CrossRef
29.
Zurück zum Zitat Johansson A, Lau J, Sandberg M, Borg LA, Magnusson PU, Carlsson PO. Endothelial cell signalling supports pancreatic beta cell function in the rat. Diabetologia. 2009;52(11):2385–94.CrossRef Johansson A, Lau J, Sandberg M, Borg LA, Magnusson PU, Carlsson PO. Endothelial cell signalling supports pancreatic beta cell function in the rat. Diabetologia. 2009;52(11):2385–94.CrossRef
30.
Zurück zum Zitat Cohrs CM, Chen C, Jahn SR, Stertmann J, Chmelova H, Weitz J, et al. Vessel network architecture of adult human islets promotes distinct cell-cell interactions in situ and is altered after transplantation. Endocrinology. 2017;158(5):1373–85.CrossRef Cohrs CM, Chen C, Jahn SR, Stertmann J, Chmelova H, Weitz J, et al. Vessel network architecture of adult human islets promotes distinct cell-cell interactions in situ and is altered after transplantation. Endocrinology. 2017;158(5):1373–85.CrossRef
31.
Zurück zum Zitat Otonkoski T, Banerjee M, Korsgren O, Thornell LE, Virtanen I. Unique basement membrane structure of human pancreatic islets: implications for beta-cell growth and differentiation. Diabetes Obes Metab. 2008;10(Suppl 4):119–27.CrossRef Otonkoski T, Banerjee M, Korsgren O, Thornell LE, Virtanen I. Unique basement membrane structure of human pancreatic islets: implications for beta-cell growth and differentiation. Diabetes Obes Metab. 2008;10(Suppl 4):119–27.CrossRef
32.
Zurück zum Zitat Lavallard V, Armanet M, Parnaud G, Meyer J, Barbieux C, Montanari E, et al. Cell rearrangement in transplanted human islets. FASEB J. 2016;30(2):748–60.CrossRef Lavallard V, Armanet M, Parnaud G, Meyer J, Barbieux C, Montanari E, et al. Cell rearrangement in transplanted human islets. FASEB J. 2016;30(2):748–60.CrossRef
33.
Zurück zum Zitat Bogdani M, Korpos E, Simeonovic CJ, Parish CR, Sorokin L, Wight TN. Extracellular matrix components in the pathogenesis of type 1 diabetes. Curr Diab Rep. 2014;14(12):552.CrossRef Bogdani M, Korpos E, Simeonovic CJ, Parish CR, Sorokin L, Wight TN. Extracellular matrix components in the pathogenesis of type 1 diabetes. Curr Diab Rep. 2014;14(12):552.CrossRef
34.
Zurück zum Zitat Bogdani M, Johnson PY, Potter-Perigo S, Nagy N, Day AJ, Bollyky PL, et al. Hyaluronan and hyaluronan-binding proteins accumulate in both human type 1 diabetic islets and lymphoid tissues and associate with inflammatory cells in insulitis. Diabetes. 2014;63(8):2727–43.CrossRef Bogdani M, Johnson PY, Potter-Perigo S, Nagy N, Day AJ, Bollyky PL, et al. Hyaluronan and hyaluronan-binding proteins accumulate in both human type 1 diabetic islets and lymphoid tissues and associate with inflammatory cells in insulitis. Diabetes. 2014;63(8):2727–43.CrossRef
35.
Zurück zum Zitat Simeonovic CJ, Popp SK, Starrs LM, Brown DJ, Ziolkowski AF, Ludwig B, et al. Loss of intra-islet heparan sulfate is a highly sensitive marker of type 1 diabetes progression in humans. PLoS One. 2018;13(2):e0191360.CrossRef Simeonovic CJ, Popp SK, Starrs LM, Brown DJ, Ziolkowski AF, Ludwig B, et al. Loss of intra-islet heparan sulfate is a highly sensitive marker of type 1 diabetes progression in humans. PLoS One. 2018;13(2):e0191360.CrossRef
36.
Zurück zum Zitat Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97(6):512–23.CrossRef Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97(6):512–23.CrossRef
37.
Zurück zum Zitat Lindahl P, Johansson BR, Leveen P, Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science. 1997;277(5323):242–5.CrossRef Lindahl P, Johansson BR, Leveen P, Betsholtz C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science. 1997;277(5323):242–5.CrossRef
38.
Zurück zum Zitat von Tell D, Armulik A, Betsholtz C. Pericytes and vascular stability. Exp Cell Res. 2006;312(5):623–9.CrossRef von Tell D, Armulik A, Betsholtz C. Pericytes and vascular stability. Exp Cell Res. 2006;312(5):623–9.CrossRef
39.
Zurück zum Zitat Richards OC, Raines SM, Attie AD. The role of blood vessels, endothelial cells, and vascular pericytes in insulin secretion and peripheral insulin action. Endocr Rev. 2010;31(3):343–63.CrossRef Richards OC, Raines SM, Attie AD. The role of blood vessels, endothelial cells, and vascular pericytes in insulin secretion and peripheral insulin action. Endocr Rev. 2010;31(3):343–63.CrossRef
40.
Zurück zum Zitat Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro-Oncology. 2005;7(4):452–64.CrossRef Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance. Neuro-Oncology. 2005;7(4):452–64.CrossRef
41.
Zurück zum Zitat Tang SC, Chiu YC, Hsu CT, Peng SJ, Fu YY. Plasticity of Schwann cells and pericytes in response to islet injury in mice. Diabetologia. 2013;56(11):2424–34.CrossRef Tang SC, Chiu YC, Hsu CT, Peng SJ, Fu YY. Plasticity of Schwann cells and pericytes in response to islet injury in mice. Diabetologia. 2013;56(11):2424–34.CrossRef
42.
Zurück zum Zitat • Juang JH, Kuo CH, Peng SJ, Tang SC. 3-D Imaging Reveals Participation of Donor Islet Schwann Cells and Pericytes in Islet Transplantation and Graft Neurovascular Regeneration. EBioMedicine. 2015;2(2):109–19. Applies cell tracing to illustrate the participation of glial cells and pericytes in islet transplantation. CrossRef • Juang JH, Kuo CH, Peng SJ, Tang SC. 3-D Imaging Reveals Participation of Donor Islet Schwann Cells and Pericytes in Islet Transplantation and Graft Neurovascular Regeneration. EBioMedicine. 2015;2(2):109–19. Applies cell tracing to illustrate the participation of glial cells and pericytes in islet transplantation. CrossRef
43.
Zurück zum Zitat Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3(3):301–13.CrossRef Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3(3):301–13.CrossRef
44.
Zurück zum Zitat Hayden MR, Karuparthi PR, Habibi J, Lastra G, Patel K, Wasekar C, et al. Ultrastructure of islet microcirculation, pericytes and the islet exocrine interface in the HIP rat model of diabetes. Exp Biol Med (Maywood). 2008;233(9):1109–23.CrossRef Hayden MR, Karuparthi PR, Habibi J, Lastra G, Patel K, Wasekar C, et al. Ultrastructure of islet microcirculation, pericytes and the islet exocrine interface in the HIP rat model of diabetes. Exp Biol Med (Maywood). 2008;233(9):1109–23.CrossRef
45.
Zurück zum Zitat Hayden MR, Karuparthi PR, Habibi J, Wasekar C, Lastra G, Manrique C, et al. Ultrastructural islet study of early fibrosis in the Ren2 rat model of hypertension. Emerging role of the islet pancreatic pericyte-stellate cell. JOP. 2007;8(6):725–38.PubMed Hayden MR, Karuparthi PR, Habibi J, Wasekar C, Lastra G, Manrique C, et al. Ultrastructural islet study of early fibrosis in the Ren2 rat model of hypertension. Emerging role of the islet pancreatic pericyte-stellate cell. JOP. 2007;8(6):725–38.PubMed
46.
Zurück zum Zitat Nakamura M, Kitamura H, Konishi S, Nishimura M, Ono J, Ina K, et al. The endocrine pancreas of spontaneously diabetic db/db mice: microangiopathy as revealed by transmission electron microscopy. Diabetes Res Clin Pract. 1995;30(2):89–100.CrossRef Nakamura M, Kitamura H, Konishi S, Nishimura M, Ono J, Ina K, et al. The endocrine pancreas of spontaneously diabetic db/db mice: microangiopathy as revealed by transmission electron microscopy. Diabetes Res Clin Pract. 1995;30(2):89–100.CrossRef
47.
Zurück zum Zitat Pietras K, Hanahan D. A multitargeted, metronomic, and maximum-tolerated dose “chemo-switch” regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer. J Clin Oncol. 2005;23(5):939–52.CrossRef Pietras K, Hanahan D. A multitargeted, metronomic, and maximum-tolerated dose “chemo-switch” regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer. J Clin Oncol. 2005;23(5):939–52.CrossRef
48.
Zurück zum Zitat • Epshtein A, Rachi E, Sakhneny L, Mizrachi S, Baer D, Landsman L. Neonatal pancreatic pericytes support beta-cell proliferation. Mol Metab. 2017;6(10):1330–8. References 48-50 are a series of three papers to investigate the influence of pericytes on β-cells. CrossRef • Epshtein A, Rachi E, Sakhneny L, Mizrachi S, Baer D, Landsman L. Neonatal pancreatic pericytes support beta-cell proliferation. Mol Metab. 2017;6(10):1330–8. References 48-50 are a series of three papers to investigate the influence of pericytes on β-cells. CrossRef
49.
Zurück zum Zitat • Sasson A, Rachi E, Sakhneny L, Baer D, Lisnyansky M, Epshtein A, et al. Islet Pericytes Are Required for beta-Cell Maturity. Diabetes. 2016;65(10):3008–14.CrossRef • Sasson A, Rachi E, Sakhneny L, Baer D, Lisnyansky M, Epshtein A, et al. Islet Pericytes Are Required for beta-Cell Maturity. Diabetes. 2016;65(10):3008–14.CrossRef
50.
Zurück zum Zitat • Sakhneny L, Rachi E, Epshtein A, Guez HC, Wald-Altman S, Lisnyansky M, et al. Pancreatic pericytes support beta-cell function in a Tcf7l2-dependent manner. Diabetes. 2018;67(3):437–47.CrossRef • Sakhneny L, Rachi E, Epshtein A, Guez HC, Wald-Altman S, Lisnyansky M, et al. Pancreatic pericytes support beta-cell function in a Tcf7l2-dependent manner. Diabetes. 2018;67(3):437–47.CrossRef
51.
Zurück zum Zitat Taborsky GJ Jr, Mundinger TO. Minireview: The role of the autonomic nervous system in mediating the glucagon response to hypoglycemia. Endocrinology. 2012;153(3):1055–62.CrossRef Taborsky GJ Jr, Mundinger TO. Minireview: The role of the autonomic nervous system in mediating the glucagon response to hypoglycemia. Endocrinology. 2012;153(3):1055–62.CrossRef
52.
Zurück zum Zitat Tang SC, Peng SJ, Chien HJ. Imaging of the islet neural network. Diabetes Obes Metab. 2014;16(Suppl 1):77–86.CrossRef Tang SC, Peng SJ, Chien HJ. Imaging of the islet neural network. Diabetes Obes Metab. 2014;16(Suppl 1):77–86.CrossRef
53.
Zurück zum Zitat • Tang SC, Shen CN, Lin PY, Peng SJ, Chien HJ, Chou YH, et al. Pancreatic neuro-insular network in young mice revealed by 3D panoramic histology. Diabetologia. 2018;61(1):158–67. References 53 and 54 are back-to-back papers to illustrate the neuro-insular network in mice and humans.CrossRef • Tang SC, Shen CN, Lin PY, Peng SJ, Chien HJ, Chou YH, et al. Pancreatic neuro-insular network in young mice revealed by 3D panoramic histology. Diabetologia. 2018;61(1):158–67. References 53 and 54 are back-to-back papers to illustrate the neuro-insular network in mice and humans.CrossRef
54.
Zurück zum Zitat • Tang SC, Baeyens L, Shen CN, Peng SJ, Chien HJ, Scheel DW, et al. Human pancreatic neuro-insular network in health and fatty infiltration. Diabetologia. 2018;61(1):168–81.CrossRef • Tang SC, Baeyens L, Shen CN, Peng SJ, Chien HJ, Scheel DW, et al. Human pancreatic neuro-insular network in health and fatty infiltration. Diabetologia. 2018;61(1):168–81.CrossRef
55.
Zurück zum Zitat Ahren B. Autonomic regulation of islet hormone secretion--implications for health and disease. Diabetologia. 2000;43(4):393–410.CrossRef Ahren B. Autonomic regulation of islet hormone secretion--implications for health and disease. Diabetologia. 2000;43(4):393–410.CrossRef
56.
Zurück zum Zitat Teff KL. Cephalic phase pancreatic polypeptide responses to liquid and solid stimuli in humans. Physiol Behav. 2010;99(3):317–23.CrossRef Teff KL. Cephalic phase pancreatic polypeptide responses to liquid and solid stimuli in humans. Physiol Behav. 2010;99(3):317–23.CrossRef
57.
Zurück zum Zitat Teff KL. How neural mediation of anticipatory and compensatory insulin release helps us tolerate food. Physiol Behav. 2011;103(1):44–50.CrossRef Teff KL. How neural mediation of anticipatory and compensatory insulin release helps us tolerate food. Physiol Behav. 2011;103(1):44–50.CrossRef
58.
Zurück zum Zitat Ahren B, Holst JJ. The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes. 2001;50(5):1030–8.CrossRef Ahren B, Holst JJ. The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes. 2001;50(5):1030–8.CrossRef
59.
Zurück zum Zitat Havel PJ, Mundinger TO, Taborsky GJ Jr. Pancreatic sympathetic nerves contribute to increased glucagon secretion during severe hypoglycemia in dogs. Am J Phys. 1996;270(1 Pt 1):E20–6. Havel PJ, Mundinger TO, Taborsky GJ Jr. Pancreatic sympathetic nerves contribute to increased glucagon secretion during severe hypoglycemia in dogs. Am J Phys. 1996;270(1 Pt 1):E20–6.
60.
Zurück zum Zitat • Butterworth E, Dickerson W, Vijay V, Weitzel K, Cooper J, Atkinson EW, et al. High Resolution 3D Imaging of the Human Pancreas Neuro-insular Network. J Vis Exp. 2018;(131):56859. The neuro-insular network in humans by tissue optical clearing and 3D light-sheet microscopy. • Butterworth E, Dickerson W, Vijay V, Weitzel K, Cooper J, Atkinson EW, et al. High Resolution 3D Imaging of the Human Pancreas Neuro-insular Network. J Vis Exp. 2018;(131):56859. The neuro-insular network in humans by tissue optical clearing and 3D light-sheet microscopy.
61.
Zurück zum Zitat Taborsky GJ Jr. Islets have a lot of nerve! Or do they? Cell Metab. 2011;14(1):5–6.CrossRef Taborsky GJ Jr. Islets have a lot of nerve! Or do they? Cell Metab. 2011;14(1):5–6.CrossRef
62.
Zurück zum Zitat Rodriguez-Diaz R, Abdulreda MH, Formoso AL, Gans I, Ricordi C, Berggren PO, et al. Innervation patterns of autonomic axons in the human endocrine pancreas. Cell Metab. 2011;14(1):45–54.CrossRef Rodriguez-Diaz R, Abdulreda MH, Formoso AL, Gans I, Ricordi C, Berggren PO, et al. Innervation patterns of autonomic axons in the human endocrine pancreas. Cell Metab. 2011;14(1):45–54.CrossRef
63.
Zurück zum Zitat Borden P, Houtz J, Leach SD, Kuruvilla R. Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation. Cell Rep. 2013;4(2):287–301.CrossRef Borden P, Houtz J, Leach SD, Kuruvilla R. Sympathetic innervation during development is necessary for pancreatic islet architecture and functional maturation. Cell Rep. 2013;4(2):287–301.CrossRef
64.
Zurück zum Zitat Ahren B. Islet nerves in focus--defining their neurobiological and clinical role. Diabetologia. 2012;55(12):3152–4.CrossRef Ahren B. Islet nerves in focus--defining their neurobiological and clinical role. Diabetologia. 2012;55(12):3152–4.CrossRef
65.
Zurück zum Zitat Rutter GA, Hodson DJ. Minireview: intraislet regulation of insulin secretion in humans. Mol Endocrinol. 2013;27(12):1984–95.CrossRef Rutter GA, Hodson DJ. Minireview: intraislet regulation of insulin secretion in humans. Mol Endocrinol. 2013;27(12):1984–95.CrossRef
66.
Zurück zum Zitat Satin LS, Butler PC, Ha J, Sherman AS. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes. Mol Asp Med. 2015;42:61–77.CrossRef Satin LS, Butler PC, Ha J, Sherman AS. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes. Mol Asp Med. 2015;42:61–77.CrossRef
67.
Zurück zum Zitat Schuit FC, Pipeleers DG. Differences in adrenergic recognition by pancreatic A and B cells. Science. 1986;232(4752):875–7.CrossRef Schuit FC, Pipeleers DG. Differences in adrenergic recognition by pancreatic A and B cells. Science. 1986;232(4752):875–7.CrossRef
68.
Zurück zum Zitat Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev. 2004;25(4):612–28.CrossRef Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev. 2004;25(4):612–28.CrossRef
69.
Zurück zum Zitat Chiu YC, Hua TE, Fu YY, Pasricha PJ, Tang SC. 3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury. Diabetologia. 2012;55(12):3252–61.CrossRef Chiu YC, Hua TE, Fu YY, Pasricha PJ, Tang SC. 3-D imaging and illustration of the perfusive mouse islet sympathetic innervation and its remodelling in injury. Diabetologia. 2012;55(12):3252–61.CrossRef
70.
Zurück zum Zitat Sunami E, Kanazawa H, Hashizume H, Takeda M, Hatakeyama K, Ushiki T. Morphological characteristics of Schwann cells in the islets of Langerhans of the murine pancreas. Arch Histol Cytol. 2001;64(2):191–201.CrossRef Sunami E, Kanazawa H, Hashizume H, Takeda M, Hatakeyama K, Ushiki T. Morphological characteristics of Schwann cells in the islets of Langerhans of the murine pancreas. Arch Histol Cytol. 2001;64(2):191–201.CrossRef
71.
Zurück zum Zitat Winer S, Tsui H, Lau A, Song A, Li X, Cheung RK, et al. Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive. Nat Med. 2003;9(2):198–205.CrossRef Winer S, Tsui H, Lau A, Song A, Li X, Cheung RK, et al. Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive. Nat Med. 2003;9(2):198–205.CrossRef
72.
Zurück zum Zitat Donev SR. Ultrastructural evidence for the presence of a glial sheath investing the islets of Langerhans in the pancreas of mammals. Cell Tissue Res. 1984;237(2):343–8.CrossRef Donev SR. Ultrastructural evidence for the presence of a glial sheath investing the islets of Langerhans in the pancreas of mammals. Cell Tissue Res. 1984;237(2):343–8.CrossRef
73.
Zurück zum Zitat Mwangi S, Anitha M, Mallikarjun C, Ding X, Hara M, Parsadanian A, et al. Glial cell line-derived neurotrophic factor increases beta-cell mass and improves glucose tolerance. Gastroenterology. 2008;134(3):727–37.CrossRef Mwangi S, Anitha M, Mallikarjun C, Ding X, Hara M, Parsadanian A, et al. Glial cell line-derived neurotrophic factor increases beta-cell mass and improves glucose tolerance. Gastroenterology. 2008;134(3):727–37.CrossRef
74.
Zurück zum Zitat Abadpour S, Gopel SO, Schive SW, Korsgren O, Foss A, Scholz H. Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis. Sci Rep. 2017;7(1):1575.CrossRef Abadpour S, Gopel SO, Schive SW, Korsgren O, Foss A, Scholz H. Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis. Sci Rep. 2017;7(1):1575.CrossRef
75.
Zurück zum Zitat Nave KA, Trapp BD. Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci. 2008;31:535–61.CrossRef Nave KA, Trapp BD. Axon-glial signaling and the glial support of axon function. Annu Rev Neurosci. 2008;31:535–61.CrossRef
76.
Zurück zum Zitat Fawcett JW, Asher RA. The glial scar and central nervous system repair. Brain Res Bull. 1999;49(6):377–91.CrossRef Fawcett JW, Asher RA. The glial scar and central nervous system repair. Brain Res Bull. 1999;49(6):377–91.CrossRef
77.
Zurück zum Zitat Pekny M, Nilsson M. Astrocyte activation and reactive gliosis. Glia. 2005;50(4):427–34.CrossRef Pekny M, Nilsson M. Astrocyte activation and reactive gliosis. Glia. 2005;50(4):427–34.CrossRef
78.
Zurück zum Zitat Teitelman G, Guz Y, Ivkovic S, Ehrlich M. Islet injury induces neurotrophin expression in pancreatic cells and reactive gliosis of peri-islet Schwann cells. J Neurobiol. 1998;34(4):304–18.CrossRef Teitelman G, Guz Y, Ivkovic S, Ehrlich M. Islet injury induces neurotrophin expression in pancreatic cells and reactive gliosis of peri-islet Schwann cells. J Neurobiol. 1998;34(4):304–18.CrossRef
79.
Zurück zum Zitat Yantha J, Tsui H, Winer S, Song A, Wu P, Paltser G, et al. Unexpected acceleration of type 1 diabetes by transgenic expression of B7-H1 in NOD mouse peri-islet glia. Diabetes. 2010;59(10):2588–96.CrossRef Yantha J, Tsui H, Winer S, Song A, Wu P, Paltser G, et al. Unexpected acceleration of type 1 diabetes by transgenic expression of B7-H1 in NOD mouse peri-islet glia. Diabetes. 2010;59(10):2588–96.CrossRef
80.
Zurück zum Zitat Pang Z, Kushiyama A, Sun J, Kikuchi T, Yamazaki H, Iwamoto Y, et al. Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes. FASEB J. 2017;31(9):4053–63.CrossRef Pang Z, Kushiyama A, Sun J, Kikuchi T, Yamazaki H, Iwamoto Y, et al. Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes. FASEB J. 2017;31(9):4053–63.CrossRef
81.
Zurück zum Zitat Foster ED, Bridges ND, Feurer ID, Eggerman TL, Hunsicker LG, Alejandro R. Improved health-related quality of life in a phase 3 islet transplantation trial in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 2018;41(5):1001–8.CrossRef Foster ED, Bridges ND, Feurer ID, Eggerman TL, Hunsicker LG, Alejandro R. Improved health-related quality of life in a phase 3 islet transplantation trial in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 2018;41(5):1001–8.CrossRef
82.
Zurück zum Zitat Schuetz C, Anazawa T, Cross SE, Labriola L, Meier RPH, Redfield RR 3rd, et al. Beta cell replacement therapy: the next 10 years. Transplantation. 2018;102(2):215–29.CrossRef Schuetz C, Anazawa T, Cross SE, Labriola L, Meier RPH, Redfield RR 3rd, et al. Beta cell replacement therapy: the next 10 years. Transplantation. 2018;102(2):215–29.CrossRef
83.
Zurück zum Zitat Webb MA, Illouz SC, Pollard CA, Gregory R, Mayberry JF, Tordoff SG, et al. Islet auto transplantation following total pancreatectomy: a long-term assessment of graft function. Pancreas. 2008;37(3):282–7.CrossRef Webb MA, Illouz SC, Pollard CA, Gregory R, Mayberry JF, Tordoff SG, et al. Islet auto transplantation following total pancreatectomy: a long-term assessment of graft function. Pancreas. 2008;37(3):282–7.CrossRef
84.
Zurück zum Zitat Wilson GC, Sutton JM, Abbott DE, Smith MT, Lowy AM, Matthews JB, et al. Long-term outcomes after total pancreatectomy and islet cell autotransplantation: is it a durable operation? Ann Surg. 2014;260(4):659–65 discussion 665–7.CrossRef Wilson GC, Sutton JM, Abbott DE, Smith MT, Lowy AM, Matthews JB, et al. Long-term outcomes after total pancreatectomy and islet cell autotransplantation: is it a durable operation? Ann Surg. 2014;260(4):659–65 discussion 665–7.CrossRef
85.
Zurück zum Zitat Vajkoczy P, Olofsson AM, Lehr HA, Leiderer R, Hammersen F, Arfors KE, et al. Histogenesis and ultrastructure of pancreatic islet graft microvasculature. Evidence for graft revascularization by endothelial cells of host origin. Am J Pathol. 1995;146(6):1397–405.PubMedPubMedCentral Vajkoczy P, Olofsson AM, Lehr HA, Leiderer R, Hammersen F, Arfors KE, et al. Histogenesis and ultrastructure of pancreatic islet graft microvasculature. Evidence for graft revascularization by endothelial cells of host origin. Am J Pathol. 1995;146(6):1397–405.PubMedPubMedCentral
86.
Zurück zum Zitat Persson-Sjogren S, Forsgren S, Taljedal IB. Peptides and other neuronal markers in transplanted pancreatic islets. Peptides. 2000;21(5):741–52.CrossRef Persson-Sjogren S, Forsgren S, Taljedal IB. Peptides and other neuronal markers in transplanted pancreatic islets. Peptides. 2000;21(5):741–52.CrossRef
87.
Zurück zum Zitat Jansson L, Carlsson PO. Graft vascular function after transplantation of pancreatic islets. Diabetologia. 2002;45(6):749–63.CrossRef Jansson L, Carlsson PO. Graft vascular function after transplantation of pancreatic islets. Diabetologia. 2002;45(6):749–63.CrossRef
88.
Zurück zum Zitat Brissova M, Fowler M, Wiebe P, Shostak A, Shiota M, Radhika A, et al. Intraislet endothelial cells contribute to revascularization of transplanted pancreatic islets. Diabetes. 2004;53(5):1318–25.CrossRef Brissova M, Fowler M, Wiebe P, Shostak A, Shiota M, Radhika A, et al. Intraislet endothelial cells contribute to revascularization of transplanted pancreatic islets. Diabetes. 2004;53(5):1318–25.CrossRef
89.
Zurück zum Zitat Pisania A, Weir GC, O'Neil JJ, Omer A, Tchipashvili V, Lei J, et al. Quantitative analysis of cell composition and purity of human pancreatic islet preparations. Lab Investig. 2010;90(11):1661–75.CrossRef Pisania A, Weir GC, O'Neil JJ, Omer A, Tchipashvili V, Lei J, et al. Quantitative analysis of cell composition and purity of human pancreatic islet preparations. Lab Investig. 2010;90(11):1661–75.CrossRef
90.
Zurück zum Zitat Mwangi SM, Usta Y, Shahnavaz N, Joseph I, Avila J, Cano J, et al. Glial cell line-derived neurotrophic factor enhances human islet posttransplantation survival. Transplantation. 2011;92(7):745–51.CrossRef Mwangi SM, Usta Y, Shahnavaz N, Joseph I, Avila J, Cano J, et al. Glial cell line-derived neurotrophic factor enhances human islet posttransplantation survival. Transplantation. 2011;92(7):745–51.CrossRef
91.
Zurück zum Zitat Shimoda M, Chen S, Noguchi H, Matsumoto S, Grayburn PA. In vivo non-viral gene delivery of human vascular endothelial growth factor improves revascularisation and restoration of euglycaemia after human islet transplantation into mouse liver. Diabetologia. 2010;53(8):1669–79.CrossRef Shimoda M, Chen S, Noguchi H, Matsumoto S, Grayburn PA. In vivo non-viral gene delivery of human vascular endothelial growth factor improves revascularisation and restoration of euglycaemia after human islet transplantation into mouse liver. Diabetologia. 2010;53(8):1669–79.CrossRef
92.
Zurück zum Zitat Su D, Zhang N, He J, Qu S, Slusher S, Bottino R, et al. Angiopoietin-1 production in islets improves islet engraftment and protects islets from cytokine-induced apoptosis. Diabetes. 2007;56(9):2274–83.CrossRef Su D, Zhang N, He J, Qu S, Slusher S, Bottino R, et al. Angiopoietin-1 production in islets improves islet engraftment and protects islets from cytokine-induced apoptosis. Diabetes. 2007;56(9):2274–83.CrossRef
93.
Zurück zum Zitat Cantaluppi V, Biancone L, Romanazzi GM, Figliolini F, Beltramo S, Ninniri MS, et al. Antiangiogenic and immunomodulatory effects of rapamycin on islet endothelium: relevance for islet transplantation. Am J Transplant. 2006;6(11):2601–11.CrossRef Cantaluppi V, Biancone L, Romanazzi GM, Figliolini F, Beltramo S, Ninniri MS, et al. Antiangiogenic and immunomodulatory effects of rapamycin on islet endothelium: relevance for islet transplantation. Am J Transplant. 2006;6(11):2601–11.CrossRef
94.
Zurück zum Zitat Berney T, Secchi A. Rapamycin in islet transplantation: friend or foe? Transpl Int. 2009;22(2):153–61.CrossRef Berney T, Secchi A. Rapamycin in islet transplantation: friend or foe? Transpl Int. 2009;22(2):153–61.CrossRef
95.
Zurück zum Zitat Juang JH, Peng SJ, Kuo CH, Tang SC. Three-dimensional islet graft histology: panoramic imaging of neural plasticity in sympathetic reinnervation of transplanted islets under the kidney capsule. Am J Physiol Endocrinol Metab. 2014;306(5):E559–70.CrossRef Juang JH, Peng SJ, Kuo CH, Tang SC. Three-dimensional islet graft histology: panoramic imaging of neural plasticity in sympathetic reinnervation of transplanted islets under the kidney capsule. Am J Physiol Endocrinol Metab. 2014;306(5):E559–70.CrossRef
96.
Zurück zum Zitat Norvell JE, Anderson JM. Assessment of possible parasympathetic innervation of the kidney. J Auton Nerv Syst. 1983;8(3):291–4.CrossRef Norvell JE, Anderson JM. Assessment of possible parasympathetic innervation of the kidney. J Auton Nerv Syst. 1983;8(3):291–4.CrossRef
97.
Zurück zum Zitat van Amsterdam WA, Blankestijn PJ, Goldschmeding R, Bleys RL. The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study. Ann Anat. 2016;204:71–9.CrossRef van Amsterdam WA, Blankestijn PJ, Goldschmeding R, Bleys RL. The morphological substrate for Renal Denervation: Nerve distribution patterns and parasympathetic nerves. A post-mortem histological study. Ann Anat. 2016;204:71–9.CrossRef
98.
Zurück zum Zitat Wang P, Fiaschi-Taesch NM, Vasavada RC, Scott DK, Garcia-Ocana A, Stewart AF. Diabetes mellitus--advances and challenges in human beta-cell proliferation. Nat Rev Endocrinol. 2015;11(4):201–12.CrossRef Wang P, Fiaschi-Taesch NM, Vasavada RC, Scott DK, Garcia-Ocana A, Stewart AF. Diabetes mellitus--advances and challenges in human beta-cell proliferation. Nat Rev Endocrinol. 2015;11(4):201–12.CrossRef
Metadaten
Titel
The Role of Accessory Cells in Islet Homeostasis
verfasst von
Shiue-Cheng Tang
Claire F. Jessup
Martha Campbell-Thompson
Publikationsdatum
01.11.2018
Verlag
Springer US
Erschienen in
Current Diabetes Reports / Ausgabe 11/2018
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-018-1096-z

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