Effect of Pituitary Adenylate Cyclase-Activating Polypeptide in Islet Transplantation

Y. Sakuma, Camillo Ricordi, A. Miki, T. Yamamoto, A. Mita, S. Barker, Ruth Molano, A. Pileggi, Y. Yasuda, T. Yada, H. Ichii

Research output: Contribution to journalArticle

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Abstract

Introduction: Pituitary adenylate cyclase-activating polypeptide (PACAP) is an islet substance serving as an intra-islet amplifier of glucose-induced insulin secretion similar to exendin-4. It has been reported that systemic administration of PACAP maintained beta-cell mass, delayed the onset of hyperglycemia, and protected beta cells from glucose toxicity. Moreover, PACAP increases glucose-stimulated insulin release in vitro and in vivo. In this study, we investigated the possibility of PACAP use in human islet transplantation. Methods: Human islets were cultured in the presence or absence of PACAP (10-12 mol/L) for 48 hours. We assessed beta-cell viability using FACS, cellular composition analysis by iCys/LSC, and glucose-stimulated insulin secretion. In vivo, islets were transplanted beneath the kidney capsule of Streptozotocin-induced diabetic immunodeficient mice. An intravenous glucose tolerance test (IVGTT) was also performed in the presence or absence of PACAP (Peptide International, Louisville, Ky, United States; 1.3 nmol/kg). Results: There were significant improvements in terms of beta-cell viability and cellular composition between islets cultured with or without PACAP, respectively (P < .05). Moreover, glucose-stimulated insulin secretion significantly improved in islets cultured with PACAP compared with controls, respectively (P < .05). Treatment of recipient mice with PACAP resulted in beneficial effects on insulin secretion (PACAP vs control, 13.2 vs 1.9 mU/L), in IVGTT. However, no significant difference was observed in glucose levels between the 2 groups. Conclusions: Our study indicated that PACAP significantly improved beta-cell viability and survival during culture, and increased insulin secretion in vitro and in vivo. However, blood glucose levels in vivo after an IVGTT did not significantly improve, probably due to increased glucagon secretion from alpha cells. PACAP supplementation to culture medium could be of assistance to improve clinical islet transplantation outcomes.

Original languageEnglish
Pages (from-to)343-345
Number of pages3
JournalTransplantation Proceedings
Volume41
Issue number1
DOIs
StatePublished - Jan 1 2009

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Pituitary Adenylate Cyclase-Activating Polypeptide
Islets of Langerhans Transplantation
Insulin
Glucose
Cell Survival
Glucose Tolerance Test
Streptozocin
Glucagon
Hyperglycemia
Capsules
Culture Media
Blood Glucose

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Effect of Pituitary Adenylate Cyclase-Activating Polypeptide in Islet Transplantation. / Sakuma, Y.; Ricordi, Camillo; Miki, A.; Yamamoto, T.; Mita, A.; Barker, S.; Molano, Ruth; Pileggi, A.; Yasuda, Y.; Yada, T.; Ichii, H.

In: Transplantation Proceedings, Vol. 41, No. 1, 01.01.2009, p. 343-345.

Research output: Contribution to journalArticle

Sakuma, Y, Ricordi, C, Miki, A, Yamamoto, T, Mita, A, Barker, S, Molano, R, Pileggi, A, Yasuda, Y, Yada, T & Ichii, H 2009, 'Effect of Pituitary Adenylate Cyclase-Activating Polypeptide in Islet Transplantation', Transplantation Proceedings, vol. 41, no. 1, pp. 343-345. https://doi.org/10.1016/j.transproceed.2008.10.064
Sakuma, Y. ; Ricordi, Camillo ; Miki, A. ; Yamamoto, T. ; Mita, A. ; Barker, S. ; Molano, Ruth ; Pileggi, A. ; Yasuda, Y. ; Yada, T. ; Ichii, H. / Effect of Pituitary Adenylate Cyclase-Activating Polypeptide in Islet Transplantation. In: Transplantation Proceedings. 2009 ; Vol. 41, No. 1. pp. 343-345.
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AU - Miki, A.

AU - Yamamoto, T.

AU - Mita, A.

AU - Barker, S.

AU - Molano, Ruth

AU - Pileggi, A.

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AU - Ichii, H.

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