A Novel Preservation Solution Containing a JNK Inhibitory Peptide Efficiently Improves Islet Yield for Porcine Islet Isolation

Hirofumi Noguchi, Chika Miyagi-Shiohira, Yoshiki Nakashima, Nana Ebi, Eri Hamada, Yoshihito Tamaki, Kazuho Kuwae, Shinji Kitamura, Naoya Kobayashi, Issei Saitoh, Masami Watanabe

Research output: Contribution to journalArticle

Abstract

Background For islet transplantation, pancreas preservation in University of Wisconsin (UW) solution is associated with disadvantages, such as collagenase inhibition, resulting in poor islet yield and islets with poor viability. In this study, we evaluated a novel preservation solution, the extracellular-type c-Jun N-terminal kinase (JNK) inhibitor-containing (EJ) solution. Methods The EJ solution has high sodium-low potassium composition with low viscosity compared to UW solution. Moreover, EJ solution contains a recently developed JNK inhibitor from our laboratory. Results We first compared the performance of EJ solution with that of UW solution. Islet yield before and after purification was significantly higher in the EJ group than in the UW group. Second, we compared the performance of EJ solution with that of EJ solution without the JNK inhibitor (EJ-J solution). After pancreas preservation in EJ solution, JNK activity was maintained at a relatively low level during islet isolation. Islet yield before and after purification was significantly higher in the EJ group than in the EJ-J group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 61.5% and 7.7% of diabetic mice in the EJ and EJ-J groups, respectively. Moreover, EJ solution exhibited reduced inhibition of collagenase digestion compared with UW solution. Conclusions Advantages of EJ solution over UW solution were inhibition of JNK activity and reduced collagenase inhibition. EJ solution may therefore be more suitable for islet isolation than UW solution.

Original languageEnglish
Pages (from-to)344-352
Number of pages9
JournalTransplantation
Volume103
Issue number2
DOIs
Publication statusPublished - Feb 1 2019

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JNK Mitogen-Activated Protein Kinases
Swine
Peptides
Collagenases
Islets of Langerhans Transplantation
Pancreas

ASJC Scopus subject areas

  • Transplantation

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A Novel Preservation Solution Containing a JNK Inhibitory Peptide Efficiently Improves Islet Yield for Porcine Islet Isolation. / Noguchi, Hirofumi; Miyagi-Shiohira, Chika; Nakashima, Yoshiki; Ebi, Nana; Hamada, Eri; Tamaki, Yoshihito; Kuwae, Kazuho; Kitamura, Shinji; Kobayashi, Naoya; Saitoh, Issei; Watanabe, Masami.

In: Transplantation, Vol. 103, No. 2, 01.02.2019, p. 344-352.

Research output: Contribution to journalArticle

Noguchi, H, Miyagi-Shiohira, C, Nakashima, Y, Ebi, N, Hamada, E, Tamaki, Y, Kuwae, K, Kitamura, S, Kobayashi, N, Saitoh, I & Watanabe, M 2019, 'A Novel Preservation Solution Containing a JNK Inhibitory Peptide Efficiently Improves Islet Yield for Porcine Islet Isolation', Transplantation, vol. 103, no. 2, pp. 344-352. https://doi.org/10.1097/TP.0000000000002555
Noguchi, Hirofumi ; Miyagi-Shiohira, Chika ; Nakashima, Yoshiki ; Ebi, Nana ; Hamada, Eri ; Tamaki, Yoshihito ; Kuwae, Kazuho ; Kitamura, Shinji ; Kobayashi, Naoya ; Saitoh, Issei ; Watanabe, Masami. / A Novel Preservation Solution Containing a JNK Inhibitory Peptide Efficiently Improves Islet Yield for Porcine Islet Isolation. In: Transplantation. 2019 ; Vol. 103, No. 2. pp. 344-352.
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abstract = "Background For islet transplantation, pancreas preservation in University of Wisconsin (UW) solution is associated with disadvantages, such as collagenase inhibition, resulting in poor islet yield and islets with poor viability. In this study, we evaluated a novel preservation solution, the extracellular-type c-Jun N-terminal kinase (JNK) inhibitor-containing (EJ) solution. Methods The EJ solution has high sodium-low potassium composition with low viscosity compared to UW solution. Moreover, EJ solution contains a recently developed JNK inhibitor from our laboratory. Results We first compared the performance of EJ solution with that of UW solution. Islet yield before and after purification was significantly higher in the EJ group than in the UW group. Second, we compared the performance of EJ solution with that of EJ solution without the JNK inhibitor (EJ-J solution). After pancreas preservation in EJ solution, JNK activity was maintained at a relatively low level during islet isolation. Islet yield before and after purification was significantly higher in the EJ group than in the EJ-J group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 61.5{\%} and 7.7{\%} of diabetic mice in the EJ and EJ-J groups, respectively. Moreover, EJ solution exhibited reduced inhibition of collagenase digestion compared with UW solution. Conclusions Advantages of EJ solution over UW solution were inhibition of JNK activity and reduced collagenase inhibition. EJ solution may therefore be more suitable for islet isolation than UW solution.",
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AU - Miyagi-Shiohira, Chika

AU - Nakashima, Yoshiki

AU - Ebi, Nana

AU - Hamada, Eri

AU - Tamaki, Yoshihito

AU - Kuwae, Kazuho

AU - Kitamura, Shinji

AU - Kobayashi, Naoya

AU - Saitoh, Issei

AU - Watanabe, Masami

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N2 - Background For islet transplantation, pancreas preservation in University of Wisconsin (UW) solution is associated with disadvantages, such as collagenase inhibition, resulting in poor islet yield and islets with poor viability. In this study, we evaluated a novel preservation solution, the extracellular-type c-Jun N-terminal kinase (JNK) inhibitor-containing (EJ) solution. Methods The EJ solution has high sodium-low potassium composition with low viscosity compared to UW solution. Moreover, EJ solution contains a recently developed JNK inhibitor from our laboratory. Results We first compared the performance of EJ solution with that of UW solution. Islet yield before and after purification was significantly higher in the EJ group than in the UW group. Second, we compared the performance of EJ solution with that of EJ solution without the JNK inhibitor (EJ-J solution). After pancreas preservation in EJ solution, JNK activity was maintained at a relatively low level during islet isolation. Islet yield before and after purification was significantly higher in the EJ group than in the EJ-J group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 61.5% and 7.7% of diabetic mice in the EJ and EJ-J groups, respectively. Moreover, EJ solution exhibited reduced inhibition of collagenase digestion compared with UW solution. Conclusions Advantages of EJ solution over UW solution were inhibition of JNK activity and reduced collagenase inhibition. EJ solution may therefore be more suitable for islet isolation than UW solution.

AB - Background For islet transplantation, pancreas preservation in University of Wisconsin (UW) solution is associated with disadvantages, such as collagenase inhibition, resulting in poor islet yield and islets with poor viability. In this study, we evaluated a novel preservation solution, the extracellular-type c-Jun N-terminal kinase (JNK) inhibitor-containing (EJ) solution. Methods The EJ solution has high sodium-low potassium composition with low viscosity compared to UW solution. Moreover, EJ solution contains a recently developed JNK inhibitor from our laboratory. Results We first compared the performance of EJ solution with that of UW solution. Islet yield before and after purification was significantly higher in the EJ group than in the UW group. Second, we compared the performance of EJ solution with that of EJ solution without the JNK inhibitor (EJ-J solution). After pancreas preservation in EJ solution, JNK activity was maintained at a relatively low level during islet isolation. Islet yield before and after purification was significantly higher in the EJ group than in the EJ-J group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 61.5% and 7.7% of diabetic mice in the EJ and EJ-J groups, respectively. Moreover, EJ solution exhibited reduced inhibition of collagenase digestion compared with UW solution. Conclusions Advantages of EJ solution over UW solution were inhibition of JNK activity and reduced collagenase inhibition. EJ solution may therefore be more suitable for islet isolation than UW solution.

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