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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

Glucose-induced insulin secretion in unencapsulated (free) and encapsulated islets (blue diamonds and red dots, respectively). Average of experimental data for free and alginate-encapsulated mouse islets perifused in parallel using a low (3 mM; G3) → high (11 mM; G11) → low (G3) incoming glucose stimulation (plus 5 min KCl followed by G3), as shown below the x-axis. Data represent the average ± SE for three experiments performed in duplicate with ~ 50 IEQ per channel. Representative encapsulated islets used in these experiments are shown on the right.
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Fig2: Glucose-induced insulin secretion in unencapsulated (free) and encapsulated islets (blue diamonds and red dots, respectively). Average of experimental data for free and alginate-encapsulated mouse islets perifused in parallel using a low (3 mM; G3) → high (11 mM; G11) → low (G3) incoming glucose stimulation (plus 5 min KCl followed by G3), as shown below the x-axis. Data represent the average ± SE for three experiments performed in duplicate with ~ 50 IEQ per channel. Representative encapsulated islets used in these experiments are shown on the right.

Mentions: To accurately quantify the effect that microencapsulation has on the time-profile of insulin secretion from isolated islets, we first performed high-resolution parallel perifusion experiments with unencapsulated and alginate-encapsulated murine islets. Then, we used the results to validate and further calibrate our FEM-based glucose-insulin computational model. Perifusion was performed with four channels in parallel and using a low (3 mM), high (11 mM), low (3 mM) glucose step with frequent sample collection (every minute); the insulin response obtained is shown in Figure 2. To allow a clear delineation of the first-phase response, the high glucose step (G11) was maintained for 20 min, which is longer than in our previously used standard protocols [34–36]. Unencapsulated islets demonstrated a well-defined first-phase peak, followed by a second-phase plateau, with possibly a slightly rising tendency (Figure 2). This was expected, given normal functioning islets release insulin in a biphasic manner in response to a stepwise increase of glucose (e.g., a relatively quick transient spike of 5–10 min /first phase/ followed by a sustained second phase that is slower and somewhat delayed [37–40]). Responses from the encapsulated islets were similar, but slightly delayed and blunted. This was again expected, due to the impact of the encapsulating hydrogel and agrees with published reports [32,41,42].Figure 2


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)

Glucose-induced insulin secretion in unencapsulated (free) and encapsulated islets (blue diamonds and red dots, respectively). Average of experimental data for free and alginate-encapsulated mouse islets perifused in parallel using a low (3 mM; G3) → high (11 mM; G11) → low (G3) incoming glucose stimulation (plus 5 min KCl followed by G3), as shown below the x-axis. Data represent the average ± SE for three experiments performed in duplicate with ~ 50 IEQ per channel. Representative encapsulated islets used in these experiments are shown on the right.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Glucose-induced insulin secretion in unencapsulated (free) and encapsulated islets (blue diamonds and red dots, respectively). Average of experimental data for free and alginate-encapsulated mouse islets perifused in parallel using a low (3 mM; G3) → high (11 mM; G11) → low (G3) incoming glucose stimulation (plus 5 min KCl followed by G3), as shown below the x-axis. Data represent the average ± SE for three experiments performed in duplicate with ~ 50 IEQ per channel. Representative encapsulated islets used in these experiments are shown on the right.
Mentions: To accurately quantify the effect that microencapsulation has on the time-profile of insulin secretion from isolated islets, we first performed high-resolution parallel perifusion experiments with unencapsulated and alginate-encapsulated murine islets. Then, we used the results to validate and further calibrate our FEM-based glucose-insulin computational model. Perifusion was performed with four channels in parallel and using a low (3 mM), high (11 mM), low (3 mM) glucose step with frequent sample collection (every minute); the insulin response obtained is shown in Figure 2. To allow a clear delineation of the first-phase response, the high glucose step (G11) was maintained for 20 min, which is longer than in our previously used standard protocols [34–36]. Unencapsulated islets demonstrated a well-defined first-phase peak, followed by a second-phase plateau, with possibly a slightly rising tendency (Figure 2). This was expected, given normal functioning islets release insulin in a biphasic manner in response to a stepwise increase of glucose (e.g., a relatively quick transient spike of 5–10 min /first phase/ followed by a sustained second phase that is slower and somewhat delayed [37–40]). Responses from the encapsulated islets were similar, but slightly delayed and blunted. This was again expected, due to the impact of the encapsulating hydrogel and agrees with published reports [32,41,42].Figure 2

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