Glucose-stimulated insulin release: Parallel perifusion studies of free and hydrogel encapsulated human pancreatic islets

Peter Buchwald, Alejandro Tamayo-Garcia, Vita Manzoli, Alice Tomei, Cherie L. Stabler

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

To explore the effects immune-isolating encapsulation has on the insulin secretion of pancreatic islets and to improve our ability to quantitatively describe the glucose-stimulated insulin release (GSIR) of pancreatic islets, we conducted dynamic perifusion experiments with isolated human islets. Free (unencapsulated) and hydrogel encapsulated islets were perifused, in parallel, using an automated multi-channel system that allows sample collection with high temporal resolution. Results indicated that free human islets secrete less insulin per unit mass or islet equivalent (IEQ) than murine islets and with a less pronounced first-phase peak. While small microcapsules (d=700μm) caused only a slightly delayed and blunted first-phase insulin response compared to unencapsulated islets, larger capsules (d=1,800μm) completely blunted the first-phase peak and decreased the total amount of insulin released. Experimentally obtained insulin time-profiles were fitted with our complex insulin secretion computational model. This allowed further fine-tuning of the hormone-release parameters of this model, which was implemented in COMSOL Multiphysics to couple hormone secretion and nutrient consumption kinetics with diffusive and convective transport. The results of these GSIR experiments, which were also supported by computational modeling, indicate that larger capsules unavoidably lead to dampening of the first-phase insulin response and to a sustained-release type insulin secretion that can only slowly respond to changes in glucose concentration. Bioartificial pancreas type devices can provide long-term and physiologically desirable solutions only if immunoisolation and biocompatibility considerations are integrated with optimized nutrient diffusion and insulin release characteristics by design.

Original languageEnglish (US)
JournalBiotechnology and Bioengineering
DOIs
StateAccepted/In press - 2017

Fingerprint

Hydrogel
Insulin
Islets of Langerhans
Hydrogels
Glucose
Capsules
Hormones
Nutrients
Food
Biocompatibility
Encapsulation
Pancreas
Tuning
Experiments
Equipment and Supplies

Keywords

  • Alginate
  • Diabetes mellitus
  • FEM model
  • Fluid dynamics
  • Glucose-stimulated insulin secretion
  • Islet encapsulation

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Glucose-stimulated insulin release : Parallel perifusion studies of free and hydrogel encapsulated human pancreatic islets. / Buchwald, Peter; Tamayo-Garcia, Alejandro; Manzoli, Vita; Tomei, Alice; Stabler, Cherie L.

In: Biotechnology and Bioengineering, 2017.

Research output: Contribution to journalArticle

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