Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin

Kate R. Mueller, A. N. Balamurugan, Gary W. Cline, Rebecca L. Pongratz, Rebecca L. Hooper, Bradley P. Weegman, Jennifer P. Kitzmann, Michael J. Taylor, Melanie L. Graham, Henk Jan Schuurman, Klearchos K Papas

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Porcine islet xenotransplantation is considered a potential cell-based therapy for type 1 diabetes. It is currently being evaluated in diabetic nonhuman primates (NHP) to assess safety and efficacy of the islet product. However, due to a variety of distinct differences between the respective species, including the insulin secretory characteristics of islets, the suitability and predictive value of the preclinical model in the extrapolation to the clinical setting remain a critical issue. Islets isolated from human (n = 3), NHP (n = 2), adult pig (AP, n = 3), and juvenile pig (JP, n = 4) pancreata were perifused with medium at basal glucose (2.5 mm) followed by high glucose (16.7 mm) concentrations. The total glucose-stimulated insulin secretion (GSIS) was calculated from generated insulin secretion profiles. Nonhuman primate islets exhibited GSIS 3-fold higher than AP islets, while AP and JP islets exhibited GSIS 1/3 and 1/30 of human islets, respectively. The insulin content of NHP and AP islets was similar to that of human islets, whereas that of JP islets was 1/5 of human islets. Despite the fact that human, NHP, and AP islets contain similar amounts of insulin, the much higher GSIS for NHP islets than for AP and JP islets suggests the need for increased dosing of islets from JP and AP in pig-to-NHP transplantation. Porcine islet xenotransplantation to humans may require significantly higher dosing given the lower GSIS of AP islets compared to human islets.

Original languageEnglish (US)
Pages (from-to)75-81
Number of pages7
JournalXenotransplantation
Volume20
Issue number2
DOIs
StatePublished - Mar 2013
Externally publishedYes

Fingerprint

Primates
Swine
Insulin
Glucose
Heterologous Transplantation
In Vitro Techniques
Cell- and Tissue-Based Therapy
Type 1 Diabetes Mellitus
Pancreas
Transplantation
Safety

Keywords

  • human
  • islets
  • nonhuman primate
  • nutrient-stimulated insulin secretion
  • pig
  • species incompatibility

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin. / Mueller, Kate R.; Balamurugan, A. N.; Cline, Gary W.; Pongratz, Rebecca L.; Hooper, Rebecca L.; Weegman, Bradley P.; Kitzmann, Jennifer P.; Taylor, Michael J.; Graham, Melanie L.; Schuurman, Henk Jan; Papas, Klearchos K.

In: Xenotransplantation, Vol. 20, No. 2, 03.2013, p. 75-81.

Research output: Contribution to journalArticle

Mueller, KR, Balamurugan, AN, Cline, GW, Pongratz, RL, Hooper, RL, Weegman, BP, Kitzmann, JP, Taylor, MJ, Graham, ML, Schuurman, HJ & Papas, KK 2013, 'Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin', Xenotransplantation, vol. 20, no. 2, pp. 75-81. https://doi.org/10.1111/xen.12022
Mueller, Kate R. ; Balamurugan, A. N. ; Cline, Gary W. ; Pongratz, Rebecca L. ; Hooper, Rebecca L. ; Weegman, Bradley P. ; Kitzmann, Jennifer P. ; Taylor, Michael J. ; Graham, Melanie L. ; Schuurman, Henk Jan ; Papas, Klearchos K. / Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin. In: Xenotransplantation. 2013 ; Vol. 20, No. 2. pp. 75-81.
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