Horm Metab Res 2014; 46(13): 921-926
DOI: 10.1055/s-0034-1389995
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Early Effects of Liver Regeneration on Endocrine Pancreas: In Vivo Change in Islet Morphology and In Vitro Assessment of Systemic Effects on β-Cell Function and Viability in the Rat Model of Two-Thirds Hepatectomy

F. Moreau
1   Diabète et Thérapie Cellulaire EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Strasbourg, France
2   Service d’Endocrinologie et Diabète, Hôpital Civil, Hôpitaux Universitaires et Faculté de Médecine de Strasbourg, Strasbourg, France
,
E. Seyfritz
1   Diabète et Thérapie Cellulaire EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Strasbourg, France
,
F. Toti
3   EA 7293 Stress vasculaire et tissulaire en transplantation: microparticles et environnement, Strasbourg, Fédération de Médécine, Université de Strasbourg, Strasbourg, France
4   UMR-CNRS-7215, Translationelle, Strasbourg
,
S. Sigrist
1   Diabète et Thérapie Cellulaire EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Strasbourg, France
,
W. Bietigier
1   Diabète et Thérapie Cellulaire EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Strasbourg, France
,
M. Pinget
1   Diabète et Thérapie Cellulaire EA 7294, Centre Européen d’Etude du Diabète, Université de Strasbourg, Strasbourg, France
2   Service d’Endocrinologie et Diabète, Hôpital Civil, Hôpitaux Universitaires et Faculté de Médecine de Strasbourg, Strasbourg, France
,
L. Kessler
2   Service d’Endocrinologie et Diabète, Hôpital Civil, Hôpitaux Universitaires et Faculté de Médecine de Strasbourg, Strasbourg, France
3   EA 7293 Stress vasculaire et tissulaire en transplantation: microparticles et environnement, Strasbourg, Fédération de Médécine, Université de Strasbourg, Strasbourg, France
› Author Affiliations
Further Information

Publication History

received 06 December 2013

accepted after second revision 28 August 2014

Publication Date:
06 November 2014 (online)

Abstract

Liver and pancreas share key roles in glucose homeostasis. Liver regeneration is associated with systemic modifications and depends especially on pancreatic hormones. The aim of the study was to investigate the role of systemic factors released after two-thirds hepatectomy (2/3H) on early possible consequences of liver regeneration on endocrine pancreas structure and function. The pancreas and serum were harvested 1, 2, or 3 days after 2/3H or sham operation in Lewis rats. The HGF and VEGF serum concentrations and plasma microparticles levels were measured. The fate of endocrine pancreas was examined through islets histomorphometry and function in sham and 2/3H rats. β-Cell line RIN-m5F viability was assessed after 24 h of growth in media supplemented with 10% serum from 2/3H or sham rats instead of FCS. Three days after surgery, the pancreas was heavier in 2/3H compared to sham rats (0.56 vs. 0.40% of body weight, p<0.05) and the proportion of islets of intermediate size was lower in 2/3H rats (5 vs. 15%, p<0.05). Compared to Sham, sera obtained 3 days after hepatectomy were more efficient to maintain the viability of RIN-m5F cells (99 vs. 67%, p<0.01). Three days after surgery, no significant differences in serum HGF, a trend to significant increase in VEGF concentration and a significant increase in microparticles levels, were observed in 2/3H vs. sham rats (9.8 vs. 6.5 nM Phtd Ser Eq., p<0.05). Liver regeneration is associated with early effects on islets and could influence β-cell viability and function by systemic effect.

 
  • References

  • 1 Michalopoulos GK, DeFrances MC. Liver regeneration. Science 1997; 276: 60-66
  • 2 Fausto N, Campbell JS, Riehle KJ. Liver regeneration. J Hepatol 2012; 57: 692-694
  • 3 Michalopoulos G, Cianciulli HD, Novotny AR, Kligerman AD, Strom SC, Jirtle RL. Liver regeneration studies with rat hepatocytes in primary culture. Cancer Res 1982; 42: 4673-4682
  • 4 Lindroos PM, Zarnegar R, Michalopoulos GK. Hepatocyte growth factor (hepatopoietin A) rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbon tetrachloride administration. Hepatology 1991; 13: 743-750
  • 5 Taniguchi E, Sakisaka S, Matsuo K, Tanikawa K, Sata M. Expression and role of vascular endothelial growth factor in liver regeneration after partial hepatectomy in rats. J Histochem Cytochem 2001; 49: 121-130
  • 6 Michalopoulos GK. Liver regeneration. J Cell Physiol 2007; 213: 286-300
  • 7 Huang J, Rudnick DA. Elucidating the Metabolic Regulation of Liver Regeneration. Am J Pathol 2014; 184: 309-321
  • 8 Bucher ML, Swaffield MN. Regulation of hepatic regeneration in rats by synergistic action of insulin and glucagon. Proc Natl Acad Sci USA 1975; 72: 1157-1160
  • 9 Weymann A, Hartman E, Gazit V, Wang C, Glauber M, Turmelle Y, Rudnick DA. p21 is required for dextrose-mediated inhibition of mouse liver regeneration. Hepatology 2009; 50: 207-215
  • 10 Johansson M, Mattsson G, Andersson A, Jansson L, Carlsson PO. Islet endothelial cells and pancreatic beta-cell proliferation: studies in vitro and during pregnancy in adult rats. Endocrinology 2006; 147: 2315-2324
  • 11 Printz H, Göke B, Fehmann HC, Weiershausen S, Nustede R, Neurath M, Rothmund M. Partial hepatectomy affects pancreatic size and function in rats. Pancreas 1993; 8: 233-239
  • 12 Rao MS, Subbarao V. DNA synthesis in exocrine and endocrine pancreas after partial hepatectomy in Syrian golden hamsters. Experientia 1986; 42: 833-834
  • 13 Rautou PE, Bresson J, Sainte-Marie Y, Vion AC, Paradis V, Renard JM, Devue C, Heymes C, Letteron P, Elkrief L, Lebrec D, Valla D, Tedgui A, Moreau R, Boulanger CM. Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis. Gastroenterology 2012; 143: 166-176
  • 14 Morel O, Jesel L, Freyssinet JM, Toti F. Cellular mechanisms underlying the formation of circulating microparticles. Arterioscler Thromb Vasc Bio 2011; 31: 15-26
  • 15 Mause SF, Weber C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ Res 2010; 107: 1047-1057
  • 16 Higgins GM, Anderson RM. Experimental pathology of the liver restoration of the liver of the white rat following partial surgical removal. Archiv Pathol 1931; 12: 186-202
  • 17 Selzner M, Clavien PA. Failure of regeneration of the steatotic rat liver: disruption at two different levels in the regeneration pathway. Hepatology 2000; 31: 35-42
  • 18 Chintinne M, Stangé G, Denys B, In ’t Veld P, Hellemans K, Pipeleers-Marichal M, Ling Z, Pipeleers D. Contribution of postnatally formed small beta cell aggregates to functional beta cell mass in adult rat pancreas. Diabetologia 2010; 53: 2380-2388
  • 19 Sutton R, Peters M, McShane P, Gray DW, Morris PJ. Isolation of rat pancreatic islets by ductal injection of collagenase. Transplantation 1986; 42: 689-691
  • 20 Wallenius VR, Rawet H, Skrtic S, Helou K, Qiu Y, Levan G, Ekberg S, Carlsson B, Isaksson OG, Nakamura T, Jansson JO. Chromosomal localization of rat hepatocyte growth factor (Hgf) and HGF receptor (Met) and characterization of HGF receptor cDNA. Mamm Genome 1997; 8: 661-667
  • 21 Jy W, Horstman LL, Jimenez JJ, Ahn YS, Biró E, Nieuwland R, Sturk A, Dignat-George F, Sabatier F, Camoin-Jau L, Sampol J, Hugel B, Zobairi F, Freyssinet JM, Nomura S, Shet AS, Key NS, Hebbel RP. Measuring circulating cell-derived microparticles. J Thromb Haemost 2004; 2: 1842-1851
  • 22 Elayat AA, El-Naggar MM, Tahir M. An immunocytochemical and morphometric study of the rat pancreatic islets. J Anat 1995; 186: 629-637
  • 23 Chintinne M, Stangé G, Denys B, In ’t Veld P, Hellemans K, Pipeleers-Marichal M, Ling Z, Pipeleers D. Contribution of postnatally formed small beta cell aggregates to functional beta cell mass in adult rat pancreas. Diabetologia 2010; 53: 2380-2388
  • 24 Kawaguchi Y. Sox9 and programming of liver and pancreatic progenitors. J Clin Invest 2013; 123: 1881-1886
  • 25 Hirano T, Manabe T, Tobe T. Morphological and functional discrepancies in endocrine pancreas after partial hepatectomy in dogs. HPB Surg 1991; 3: 103-114
  • 26 Sudo T, Shobu R, Kuyama T, Suzuki T. Immunohistochemical changes of the islet cells of Langerhans after partial hepatectomy in dogs. Am J Gastroenterol 1986; 81: 266-271
  • 27 Butler AE, Cao-Minh L, Galasso R, Rizza RA, Corradin A, Cobelli C, Butler PC. Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy. Diabetologia 2010; 53: 2167-2176
  • 28 Hohmeier HE, Newgard CB. Cell lines derived from pancreatic islets. Mol Cell Endocrinol 2004; 228: 121-128
  • 29 Mellado-Gil J, Rosa TC, Demirci C, Gonzalez-Pertusa JA, Velazquez-Garcia S, Ernst S, Valle S, Vasavada RC, Stewart AF, Alonso LC, Garcia-Ocaña A. Disruption of hepatocyte growth factor/c-Met signaling enhances pancreatic beta-cell death and accelerates the onset of diabetes. Diabetes 2011; 60: 525-536
  • 30 Langlois A, Bietiger W, Sencier MC, Maillard E, Pinget M, Kessler L, Sigrist S. Adenoviral infection or deferoxamine? Two approaches to overexpress VEGF in beta-cell lines. J Drug Target 2009; 17: 415-422
  • 31 Witek RP, Yang L, Liu R, Jung Y, Omenetti A, Syn WK, Choi SS, Cheong Y, Fearing CM, Agboola KM, Chen W, Diehl AM. Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells. Gastroenterology 2009; 136: 320-330
  • 32 Rautou PE, Bresson J, Sainte-Marie Y, Vion AC, Paradis V, Renard JM, Devue C, Heymes C, Letteron P, Elkrief L, Lebrec D, Valla D, Tedgui A, Moreau R, Boulanger CM. Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis. Gastroenterology 2012; 143: 166-176
  • 33 Freeman CM, Quillin 3rd RC, Wilson GC, Nojima H, Johnson BL, Sutton JM, Schuster RM, Blanchard J, Edwards MJ, Caldwell CC, Lentsch AB. Characterization of microparticles after hepatic ischemia-reperfusion injury. PLoS One 2014; 9: e97945
  • 34 Constantinescu AA, Gleizes C, Alhosin M, Yala E, Zobairi F, Leclercq A, Stoian G, Mitrea IL, Prévost G, Toti F, Kessler L. Exocrine cell-derived microparticles in response to lipopolysaccharide promote endocrine dysfunction in cystic fibrosis. J Cyst Fibros 2014; 13: 219-226