Tags

Type your tag names separated by a space and hit enter

Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets.
Biomed Eng Online. 2015 Mar 28; 14:28.BE

Abstract

BACKGROUND

In type 1 diabetic patients, who have lost their ability to produce insulin, transplantation of pancreatic islet cells can normalize metabolic control in a manner that is not achievable with exogenous insulin. To be successful, this procedure has to address the problems caused by the immune and autoimmune responses to the graft. Islet encapsulation using various techniques and materials has been and is being extensively explored as a possible approach. Within this framework, it is of considerable interest to characterize the effect encapsulation has on the insulin response of pancreatic islets.

METHODS

To improve our ability to quantitatively describe the glucose-stimulated insulin release (GSIR) of pancreatic islets in general and of micro-encapsulated islets in particular, we performed dynamic perifusion experiments with frequent sampling. We used unencapsulated and microencapsulated murine islets in parallel and fitted the results with a complex local concentration-based finite element method (FEM) computational model.

RESULTS

The high-resolution dynamic perifusion experiments allowed good characterization of the first-phase and second-phase insulin secretion, and we observed a slightly delayed and blunted first-phase insulin response for microencapsulated islets when compared to free islets. Insulin secretion profiles of both free and encapsulated islets could be fitted well by a COMSOL Multiphysics model that couples hormone secretion and nutrient consumption kinetics with diffusive and convective transport. This model, which was further validated and calibrated here, can be used for arbitrary geometries and glucose stimulation sequences and is well suited for the quantitative characterization of the insulin response of cultured, perifused, transplanted, or encapsulated islets.

CONCLUSIONS

The present high-resolution GSIR experiments allowed for direct characterization of the effect microencapsulation has on the time-profile of insulin secretion. The multiphysics model, further validated here with the help of these experimental results, can be used to increase our understanding of the challenges that have to be faced in the design of bioartificial pancreas-type devices and to advance their further optimization.

Authors+Show Affiliations

Diabetes Research Institute, University of Miami, DRI, 1450 NW 10th Ave (R-134), Miami, FL, 33136, USA. pbuchwald@med.miami.edu. Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine, Miami, FL, USA. pbuchwald@med.miami.edu.Diabetes Research Institute, University of Miami, DRI, 1450 NW 10th Ave (R-134), Miami, FL, 33136, USA. SCechin@med.miami.edu.Diabetes Research Institute, University of Miami, DRI, 1450 NW 10th Ave (R-134), Miami, FL, 33136, USA. JWeaver@med.miami.edu. Biomedical Engineering, University of Miami, Miller School of Medicine, Miami, FL, USA. JWeaver@med.miami.edu.Diabetes Research Institute, University of Miami, DRI, 1450 NW 10th Ave (R-134), Miami, FL, 33136, USA. CStabler@med.miami.edu. Biomedical Engineering, University of Miami, Miller School of Medicine, Miami, FL, USA. CStabler@med.miami.edu. DeWitt-Daughtry Department of Surgery, University of Miami, Miller School of Medicine, Miami, FL, USA. CStabler@med.miami.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25889474

Citation

Buchwald, Peter, et al. "Experimental Evaluation and Computational Modeling of the Effects of Encapsulation On the Time-profile of Glucose-stimulated Insulin Release of Pancreatic Islets." Biomedical Engineering Online, vol. 14, 2015, p. 28.
Buchwald P, Cechin SR, Weaver JD, et al. Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets. Biomed Eng Online. 2015;14:28.
Buchwald, P., Cechin, S. R., Weaver, J. D., & Stabler, C. L. (2015). Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets. Biomedical Engineering Online, 14, 28. https://doi.org/10.1186/s12938-015-0021-9
Buchwald P, et al. Experimental Evaluation and Computational Modeling of the Effects of Encapsulation On the Time-profile of Glucose-stimulated Insulin Release of Pancreatic Islets. Biomed Eng Online. 2015 Mar 28;14:28. PubMed PMID: 25889474.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets. AU - Buchwald,Peter, AU - Cechin,Sirlene R, AU - Weaver,Jessica D, AU - Stabler,Cherie L, Y1 - 2015/03/28/ PY - 2014/10/01/received PY - 2015/03/03/accepted PY - 2015/4/19/entrez PY - 2015/4/19/pubmed PY - 2016/3/12/medline SP - 28 EP - 28 JF - Biomedical engineering online JO - Biomed Eng Online VL - 14 N2 - BACKGROUND: In type 1 diabetic patients, who have lost their ability to produce insulin, transplantation of pancreatic islet cells can normalize metabolic control in a manner that is not achievable with exogenous insulin. To be successful, this procedure has to address the problems caused by the immune and autoimmune responses to the graft. Islet encapsulation using various techniques and materials has been and is being extensively explored as a possible approach. Within this framework, it is of considerable interest to characterize the effect encapsulation has on the insulin response of pancreatic islets. METHODS: To improve our ability to quantitatively describe the glucose-stimulated insulin release (GSIR) of pancreatic islets in general and of micro-encapsulated islets in particular, we performed dynamic perifusion experiments with frequent sampling. We used unencapsulated and microencapsulated murine islets in parallel and fitted the results with a complex local concentration-based finite element method (FEM) computational model. RESULTS: The high-resolution dynamic perifusion experiments allowed good characterization of the first-phase and second-phase insulin secretion, and we observed a slightly delayed and blunted first-phase insulin response for microencapsulated islets when compared to free islets. Insulin secretion profiles of both free and encapsulated islets could be fitted well by a COMSOL Multiphysics model that couples hormone secretion and nutrient consumption kinetics with diffusive and convective transport. This model, which was further validated and calibrated here, can be used for arbitrary geometries and glucose stimulation sequences and is well suited for the quantitative characterization of the insulin response of cultured, perifused, transplanted, or encapsulated islets. CONCLUSIONS: The present high-resolution GSIR experiments allowed for direct characterization of the effect microencapsulation has on the time-profile of insulin secretion. The multiphysics model, further validated here with the help of these experimental results, can be used to increase our understanding of the challenges that have to be faced in the design of bioartificial pancreas-type devices and to advance their further optimization. SN - 1475-925X UR - https://www.unboundmedicine.com/medline/citation/25889474/Experimental_evaluation_and_computational_modeling_of_the_effects_of_encapsulation_on_the_time_profile_of_glucose_stimulated_insulin_release_of_pancreatic_islets_ L2 - https://biomedical-engineering-online.biomedcentral.com/articles/10.1186/s12938-015-0021-9 DB - PRIME DP - Unbound Medicine ER -