Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin
Article first published online: 5 FEB 2013
© 2013 John Wiley & Sons A/S
Volume 20, Issue 2, pages 75–81, March/April 2013
How to Cite
Differences in glucose-stimulated insulin secretion in vitro of islets from human, nonhuman primate and porcine origin. Xenotransplantation 2013; 20: 75–81. © 2013 John Wiley & Sons A/S., , , , , , , , , , .
- Issue published online: 2 APR 2013
- Article first published online: 5 FEB 2013
- Manuscript Accepted: 28 DEC 2012
- Manuscript Received: 12 SEP 2012
- nonhuman primate;
- nutrient-stimulated insulin secretion;
- species incompatibility
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.