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Histochemistry and Cell Biology

, Volume 148, Issue 4, pp 345–357 | Cite as

Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of the adult human pancreas

  • Michelle Kim
  • Perri Deacon
  • Rommel G. Tirona
  • Richard B. Kim
  • Christopher L. Pin
  • Henriette E. Meyer zu Schwabedissen
  • Rennian Wang
  • Ute I. SchwarzEmail author
Original Paper

Abstract

Organic anion-transporting polypeptides (OATPs) are membrane proteins that mediate cellular uptake of structurally diverse endogenous and exogenous compounds, including bile salts, thyroid and sex hormones, pharmacological agents, and toxins. Roles of OATPs in human liver are well established. Our recent report suggested the presence of the hepatic transporter OATP1B3 in human β cells. The aim of this study was to better characterize cellular localization and interindividual variation in OATP1B3 expression in human adult islets as a function of age, sex, and pancreatic disease, and to assess the expression of other OATPs. High transcript levels of OATP1B3, OATP2B1, OATP1A2, but not OATP1B1 were observed in isolated human adult islets. While OATP1B3 protein expression was variable, the carrier co-localized more frequently with glucagon-positive α cells than insulin-positive β cells in islets of normal pancreatic tissues from ten subjects using dual immunostaining. Moreover, OATP1B3 co-staining with endocrine cells was two- to three-fold higher in older (≥60 years) than younger (<60 years) subjects. In comparison, in a subset of three individuals, OATP2B1 was primarily found in β cells, suggesting a distinct expression pattern for OATP1B3 and OATP2B1 in islets. Abundant OATP1B3 staining was also observed in islet as well as ductal cells of diseased tissues of patients with pancreatitis or pancreatic adenocarcinoma. Considering the abundance of key OATP carriers in β and α cells, potential implications of OATP transport in islet cell function may be suggested. Future studies are needed to gain insights into their specific endocrine roles as well as pharmacological relevance.

Keywords

Membrane transporters Organic anion transport protein Human pancreas Islet Insulin secretion 

Notes

Acknowledgements

This work was supported by the Western Strategic Support for CIHR Success Seed Grant (R5193A01) of the University of Western Ontario and the Internal Research Fund (IRF) Award (LHR F0565) of the Lawson Health Research Institute, London, Ontario, Canada.

Compliance with ethical standards

Conflict of interest

No potential conflicts of interest relevant to this article were reported.

Supplementary material

418_2017_1580_MOESM1_ESM.pdf (903 kb)
Supplementary Fig. 1 Control tissue sections for immunofluorescent (IF) or immunohistochemistry stainings (IHC) of OATP1B3 and OATP2B1. a No primary antibody control for OATP1B3 stainings using pancreatic sections of 2 subjects. b Anti-OATP1B3 staining (positive control) and no primary antibody (negative) control in liver tissue sections. c Anti-OATP2B1 staining (positive control) and no primary antibody (negative) control in duodenum tissue sections derived from intestinal biopsies. (PDF 903 kb)
418_2017_1580_MOESM2_ESM.pdf (581 kb)
Supplementary Fig. 2 Specificity of OATP1B3 and OATP2B1 antibodies after heterologous expression of OATPs in HeLa cells as described in Methods. a IF staining for OATP1B3 and OATP2B1 in HeLa cells overexpressing OATPs grown on culture slides.(PDF 581 kb)
418_2017_1580_MOESM3_ESM.pdf (839 kb)
Supplementary Fig. 3 OATP1B3 immunocytochemistry staining of normal adult pancreas demonstrating ductal cell staining. OATP1B3 positive cells are highlighted with white arrows. Anti-elastin staining was performed to differentiate between pancreatic ducts (a) and blood vessels (b). (PDF 839 kb)
418_2017_1580_MOESM4_ESM.docx (18 kb)
Supplementary material 4 (DOCX 18 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Michelle Kim
    • 1
  • Perri Deacon
    • 1
  • Rommel G. Tirona
    • 1
  • Richard B. Kim
    • 1
    • 2
    • 3
  • Christopher L. Pin
    • 1
    • 3
    • 4
  • Henriette E. Meyer zu Schwabedissen
    • 5
  • Rennian Wang
    • 1
    • 2
  • Ute I. Schwarz
    • 1
    • 2
    • 6
    Email author
  1. 1.Department of Physiology and PharmacologyUniversity of Western OntarioLondonCanada
  2. 2.Department of MedicineUniversity of Western OntarioLondonCanada
  3. 3.Department of OncologyUniversity of Western OntarioLondonCanada
  4. 4.Department of PaediatricsUniversity of Western OntarioLondonCanada
  5. 5.Biopharmacy, Department of Pharmaceutical ScienceUniversity BaselBaselSwitzerland
  6. 6.Division of Clinical Pharmacology, LHSC University HospitalUniversity of Western OntarioLondonCanada

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