OATP1B3 Is Expressed in Pancreatic β-Islet Cells and Enhances the Insulinotropic Effect of the Sulfonylurea Derivative Glibenclamide

Schwabedissen, Henriette E. Meyer zu; Boettcher, Kerstin; Steiner, Tobias; Schwarz, Ute I.; Keiser, Markus; Kroemer, Heyo K.; Siegmund, Werner

doi:10.2337/db13-1005

Cited by 30 publications

(20 citation statements)

References 45 publications

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“…Organic anion transporting polypeptides OATP1B1-3 are drug transporters relevant for cellular drug entry and thus mechanism of action of most drugs [Picard et al 2010]. Recently expression of OATP1B3 was found to be in the islets of Langerhans of human pancreas, and facilitating cellular entry of glibenclamide [Meyer Zu Schwabedissen et al 2014]. Thus, OATP1B3 likely are affected by drug-drug interactions or by genetic variants, influencing efficacy of SU or Meteglinids.…”

Section: Susmentioning

confidence: 99%

Clinically and pharmacologically relevant interactions of antidiabetic drugs

May

Schindler

2016

Therapeutic Advances in Endocrinology

110

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Abstract:Patients with type 2 diabetes mellitus often require multifactorial pharmacological treatment due to different comorbidities. An increasing number of concomitantly taken medications elevate the risk of the patient experiencing adverse drug effects or drug interactions. Drug interactions can be divided into pharmacokinetic and pharmacodynamic interactions affecting cytochrome (CYP) enzymes, absorption properties, transporter activities and receptor affinities. Furthermore, nutrition, herbal supplements, patient's age and gender are of clinical importance. Relevant drug interactions are predominantly related to sulfonylureas, thiazolidinediones and glinides. Although metformin has a very low interaction potential, caution is advised when drugs that impair renal function are used concomitantly. With the exception of saxagliptin, dipeptidyl peptidase-4 (DPP-4) inhibitors also show a low interaction potential, but all drugs affecting the drug transporter P-glycoprotein should be used with caution. Incretin mimetics and sodium-glucose cotransporter-2 (SGLT-2) inhibitors comprise a very low interaction potential and are therefore recommended as an ideal combination partner from the clinical-pharmacologic point of view.

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Section: Susmentioning

confidence: 99%

Clinically and pharmacologically relevant interactions of antidiabetic drugs

May

Schindler

2016

Therapeutic Advances in Endocrinology

110

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“…This protein has the ability to transport small anion molecules including certain drugs or contrast media across the cell membrane. OATP1B3 are expressed by the cells in the liver, small intestine, and even islet cells, and in particular OATP1B3 in the islet cells can enhance the insulinotropic effect of the sulfonylurea derivative glibenclamide . Gadolinium‐ethoxybenzyl‐diethylenetriaminepentaacetic acid (Gd‐EOB‐DTPA), a clinically approved MRI contrast agent widely applied in clinical liver imaging can be transported across cell membranes mediated mainly by the OATP family, especially OATP1B1 and OATP1B3 (OATP8).…”

Section: Introductionmentioning

confidence: 99%

In vivo imaging of insulin‐secreting human pancreatic ductal cells using MRI reporter gene technique: A feasibility study

Hsiao

Liu

et al. 2019

Magnetic Resonance in Med

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Purpose The purpose of this study was to investigate the feasibility of in vivo imaging of human pancreatic ductal cells by OATP1B3 reporter gene under MRI. Methods A human cell line (PANC‐1) derived from the pancreatic ductal epithelium was used in this study. After transduction of OATP1B3, the cellular physiological functions and the ability of intracellular uptake of the MRI contrast medium (Gd‐EOB‐DTPA) were examined. Induced differentiation of the PANC‐1 cells into hormone‐secreting cells were performed to simulate pancreatic β‐like cells. The hormone‐secreting cells were implanted into rats and in vivo MRI was evaluated. Results The mRNA and proteins of OATP1B3 were highly expressed. No significant change of cellular physiological functions was found after the expression. After induced differentiation, the hormone secretion capacities of the OATP1B3‐expressing PANC‐1 cells were confirmed. Intra‐cellular uptake of Gd‐EOB‐DTPA was determined in vitro by inductively coupled plasma mass spectrometry and MRI. In vivo MRI of the OATP1B3‐expressing xenograft revealed an increased signal intensity after contrast enhancement. Conclusion OATP1B3 can be used as a safe and feasible in vivo MRI gene reporter for human pancreatic ductal cells.

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“…Although the expressions of the OATP1B1 and OATP1B3 transporters are assumed to be liver-specific, recent evidence (Meyer zu Schwabedissen et al 2014) indicated the presence of the OATP1B3 transporter in pancreatic β cells. A detailed gene expression and immunohistochemical study by Kim et al (2017) now shows high expression of OATP1B3, OATP2B1 and OATP1Al mRNA in human pancreatic islets, and a high association of OATP1B3 immunostaining with glucagon-producing pancreatic α cells.…”

Section: Oatp1b3 and Oatp2b1 Transporter Expression In Human Pancreatmentioning

confidence: 99%

In focus in HCB

Taatjes

Roth

2017

Histochem Cell Biol

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immunohistochemical expression prior to CABG procedure might serve as a predictive indicator of potential early graft failure. Thymocyte-thymic epithelial cell interactions in EphB-deficient miceEpithelial free areas (EFA) are known to occur in both the cortex and medulla of the thymus in a variety of animal species. Whether the cortical and thymic EFAs represent the same or different histological and functional situations remains open for debate. Garcia-Ceca et al. (2017) have now investigated whether EFAs might represent microenvironments where thymocyte-thymic epithelial cell (TEC) interactions are disrupted, potentially resulting in altered thymic histology. As a model system, they employed EphB-deficient mice (EphB, a family of protein tyrosine kinases, and ephrins-B, their ligands are regulators of epithelial organization) previously shown by these authors to display altered thymocyte-TEC interactions (Garcia-Ceca et al. 2015). They used multilabel fluorescence microscopy, semiquantitative analysis, and transmission electron microscopy to evaluate the number and sizes of EFAs, as well as their organization and cell content in EphB-deficient mice compared to wild-type (WT) control animals. Their morphological results showed that: (1) in both WT and EphB-deficient mice, the number and size of EFAs were larger in the medulla compared to the cortex; (2) low numbers of EFAs correlate with larger areas; (3) EFA structure and cell content are similar in WT and EphB-deficient thymuses; and (4) EFAs in cortex and medulla contain different cell types and are structurally distinct with cortical areas possessing DP thymocytes and medullary regions SP thymocytes. Overall, their results suggest that EFAs in their model may be partially due to New details for predicting saphenous vein graft occlusion following CABG surgeryCoronary artery bypass grafting (CABG) is currently the method of choice for improving blood flow in the atherosclerotic vessel through surgical procedures. In younger patients (less than 65 years of age) a segment from the internal thoracic artery is classically used as the donor vessel for the graft, whereas in patients older than 65 years of age a section from the saphenous vein is typically chosen since it is less likely to undergo arterialization (Al-Sabti et al. 2013). Although much information is known concerning factors responsible for patency rates for internal thoracic artery donor vessels, very little is currently known about those responsible for saphenous vein patency in CABG procedures. However, since stem cell and progenitor cell proliferation in the graft wall have been shown to be involved in early saphenous vein graft occlusion (Timmermans et al. 2009), Malinska et al. (2017 performed a multivariate analysis of stem cell and progenitor cell markers in the donor saphenous vein wall prior to CABG procedure, followed by correlation with graft occlusion. Their results showed that strong immunohistochemical expression of CD133 (a stem cell marker) in smooth muscle cells of the tunica media ...

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OATP1B3 Is Expressed in Pancreatic β-Islet Cells and Enhances the Insulinotropic Effect of the Sulfonylurea Derivative Glibenclamide

Cited by 30 publications

References 45 publications

Clinically and pharmacologically relevant interactions of antidiabetic drugs

Clinically and pharmacologically relevant interactions of antidiabetic drugs

In vivo imaging of insulin‐secreting human pancreatic ductal cells using MRI reporter gene technique: A feasibility study

In focus in HCB

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