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Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets.

Buchwald P, Cechin SR, Weaver JD, Stabler CL - Biomed Eng Online (2015)

Bottom Line: Within this framework, it is of considerable interest to characterize the effect encapsulation has on the insulin response of pancreatic islets.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.

View Article: PubMed Central - PubMed

Affiliation: Diabetes Research Institute, University of Miami, DRI, 1450 NW 10th Ave (R-134), Miami, FL, 33136, USA. pbuchwald@med.miami.edu.

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.

No MeSH data available.


Related in: MedlinePlus

Fit of the experimental glucose-induced insulin secretion in unencapsulated (free) and encapsulated islets perifused in parallel with the computational model. Experimental data are the same as in Figure 2; calculated insulin outflow in response to the same stepwise glucose is with the current model for capsule thicknesses of 0 (free islets) and lcaps = 150 μm assuming islet sizes as shown in Figure 5 and following a 2D to 3D conversion with a total islet volume scaled to 50 IEQ (see text).
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Fig6: Fit of the experimental glucose-induced insulin secretion in unencapsulated (free) and encapsulated islets perifused in parallel with the computational model. Experimental data are the same as in Figure 2; calculated insulin outflow in response to the same stepwise glucose is with the current model for capsule thicknesses of 0 (free islets) and lcaps = 150 μm assuming islet sizes as shown in Figure 5 and following a 2D to 3D conversion with a total islet volume scaled to 50 IEQ (see text).

Mentions: Obtained experimental insulin-release profiles could be fitted well with the present model both for the free and encapsulated islets (r2 of 0.952 and 0.853, respectively) (Figure 6). Remarkably, the total calculated outgoing flux, which requires scaling with height data to convert the 2D flux to 3D values, gave the present fit shown in Figure 6 after scaling to 50 IEQ (i.e., an islet volume of 50 × 1.77·10−13 m3) – exactly the islet equivalent (IEQ) number used in the experiments. This was particularly encouraging as it supports the accuracy of the insulin secretion rate parameter values, Rins (maximum reaction rate) and CHf,ins (the concentration corresponding to half-maximal response) (Table 1), originally derived from human data, and indicates that they can give an adequate description for murine islets as well (with the single adjustment of increasing the kinsL value, see Figure 4).Figure 6


Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets.

Buchwald P, Cechin SR, Weaver JD, Stabler CL - Biomed Eng Online (2015)

Fit of the experimental glucose-induced insulin secretion in unencapsulated (free) and encapsulated islets perifused in parallel with the computational model. Experimental data are the same as in Figure 2; calculated insulin outflow in response to the same stepwise glucose is with the current model for capsule thicknesses of 0 (free islets) and lcaps = 150 μm assuming islet sizes as shown in Figure 5 and following a 2D to 3D conversion with a total islet volume scaled to 50 IEQ (see text).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4403786&req=5

Fig6: Fit of the experimental glucose-induced insulin secretion in unencapsulated (free) and encapsulated islets perifused in parallel with the computational model. Experimental data are the same as in Figure 2; calculated insulin outflow in response to the same stepwise glucose is with the current model for capsule thicknesses of 0 (free islets) and lcaps = 150 μm assuming islet sizes as shown in Figure 5 and following a 2D to 3D conversion with a total islet volume scaled to 50 IEQ (see text).
Mentions: Obtained experimental insulin-release profiles could be fitted well with the present model both for the free and encapsulated islets (r2 of 0.952 and 0.853, respectively) (Figure 6). Remarkably, the total calculated outgoing flux, which requires scaling with height data to convert the 2D flux to 3D values, gave the present fit shown in Figure 6 after scaling to 50 IEQ (i.e., an islet volume of 50 × 1.77·10−13 m3) – exactly the islet equivalent (IEQ) number used in the experiments. This was particularly encouraging as it supports the accuracy of the insulin secretion rate parameter values, Rins (maximum reaction rate) and CHf,ins (the concentration corresponding to half-maximal response) (Table 1), originally derived from human data, and indicates that they can give an adequate description for murine islets as well (with the single adjustment of increasing the kinsL value, see Figure 4).Figure 6

Bottom Line: Within this framework, it is of considerable interest to characterize the effect encapsulation has on the insulin response of pancreatic islets.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.

View Article: PubMed Central - PubMed

Affiliation: Diabetes Research Institute, University of Miami, DRI, 1450 NW 10th Ave (R-134), Miami, FL, 33136, USA. pbuchwald@med.miami.edu.

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.

No MeSH data available.


Related in: MedlinePlus