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Transplantation of Encapsulated Pancreatic Islets as a Treatment for Patients with Type 1 Diabetes Mellitus.

Qi M - Adv Med (2014)

Bottom Line: Encapsulation of pancreatic islets has been proposed and investigated for over three decades to improve islet transplantation outcomes and to eliminate the side effects of immunosuppressive medications.Of the numerous encapsulation systems developed in the past, microencapsulation have been studied most extensively so far.A wide variety of materials has been tested for microencapsulation in various animal models (including nonhuman primates or NHPs) and some materials were shown to induce immunoprotection to islet grafts without the need for chronic immunosuppression.

View Article: PubMed Central - PubMed

Affiliation: Division of Transplantation/Department of Surgery, University of Illinois at Chicago, IL 60612, USA ; Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute of the City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.

ABSTRACT
Encapsulation of pancreatic islets has been proposed and investigated for over three decades to improve islet transplantation outcomes and to eliminate the side effects of immunosuppressive medications. Of the numerous encapsulation systems developed in the past, microencapsulation have been studied most extensively so far. A wide variety of materials has been tested for microencapsulation in various animal models (including nonhuman primates or NHPs) and some materials were shown to induce immunoprotection to islet grafts without the need for chronic immunosuppression. Despite the initial success of microcapsules in NHP models, the combined use of islet transplantation (allograft) and microencapsulation has not yet been successful in clinical trials. This review consists of three sections: introduction to islet transplantation, transplantation of encapsulated pancreatic islets as a treatment for patients with type 1 diabetes mellitus (T1DM), and present challenges and future perspectives.

No MeSH data available.


Related in: MedlinePlus

Diagram of insulin secretion from pancreatic β cells. (a) Cellular representation of an insulin-release process; (b) Graphical display of the biphasic insulin secretion.
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fig3: Diagram of insulin secretion from pancreatic β cells. (a) Cellular representation of an insulin-release process; (b) Graphical display of the biphasic insulin secretion.

Mentions: Pancreatic β cells, which constitute 65–80% of the total cells in an islet, play a fundamental role in controlling metabolism through insulin secretion. Insulin release from β cells is controlled by the β cell's electrical activity, metabolic events, and ion signaling. These sets of intricate actions display the complex kinetic profile of biphasic and pulsatile responses to real-time changes in glucose levels [72, 73]. Insulin secretion is a complex and dynamic process. Glucose catabolism generates ATP through the mitochondrial Tricarboxylic Acid Cycle (TCA cycle), which consequently closes ATP-sensitive K+  (KATP) channels, initiates plasma membrane depolarization, and increases Ca2+ concentration, through the rapid influx of Ca2+ via voltage-dependent calcium channels (VDCCs). This glucose-stimulated increase in Ca2+ concentration triggers the fusion of insulin granules with the cell membrane and the exocytosis of insulin, C-peptide, and proinsulin [74–77] (Figure 3(a)). Alternate pathways for insulin secretion, independent from KATP and Ca2+ concentrations, have been described [78, 79]. However, the KATP and Ca2+ concentration-mediated pathway remains the primary mechanism of glucose-stimulated insulin secretion. The normal response of β cells to glucose stimulation is the biphasic secretion process. The first phase corresponds to a transient and clear increase in the secretion rate. This is followed by a sharp decrease to the lowest secretion rate and a constantly flat or gradually increasing second phase that lasts as long as glucose stimulation is applied (Figure 3(b)). The secretion profiles, which are influenced by the environmental stimuli and controlled by the intrinsic characteristics of β cells, are thought to be important for insulin effects; however, the underlying mechanism of such dynamics has not been fully revealed [80, 81].


Transplantation of Encapsulated Pancreatic Islets as a Treatment for Patients with Type 1 Diabetes Mellitus.

Qi M - Adv Med (2014)

Diagram of insulin secretion from pancreatic β cells. (a) Cellular representation of an insulin-release process; (b) Graphical display of the biphasic insulin secretion.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590955&req=5

fig3: Diagram of insulin secretion from pancreatic β cells. (a) Cellular representation of an insulin-release process; (b) Graphical display of the biphasic insulin secretion.
Mentions: Pancreatic β cells, which constitute 65–80% of the total cells in an islet, play a fundamental role in controlling metabolism through insulin secretion. Insulin release from β cells is controlled by the β cell's electrical activity, metabolic events, and ion signaling. These sets of intricate actions display the complex kinetic profile of biphasic and pulsatile responses to real-time changes in glucose levels [72, 73]. Insulin secretion is a complex and dynamic process. Glucose catabolism generates ATP through the mitochondrial Tricarboxylic Acid Cycle (TCA cycle), which consequently closes ATP-sensitive K+  (KATP) channels, initiates plasma membrane depolarization, and increases Ca2+ concentration, through the rapid influx of Ca2+ via voltage-dependent calcium channels (VDCCs). This glucose-stimulated increase in Ca2+ concentration triggers the fusion of insulin granules with the cell membrane and the exocytosis of insulin, C-peptide, and proinsulin [74–77] (Figure 3(a)). Alternate pathways for insulin secretion, independent from KATP and Ca2+ concentrations, have been described [78, 79]. However, the KATP and Ca2+ concentration-mediated pathway remains the primary mechanism of glucose-stimulated insulin secretion. The normal response of β cells to glucose stimulation is the biphasic secretion process. The first phase corresponds to a transient and clear increase in the secretion rate. This is followed by a sharp decrease to the lowest secretion rate and a constantly flat or gradually increasing second phase that lasts as long as glucose stimulation is applied (Figure 3(b)). The secretion profiles, which are influenced by the environmental stimuli and controlled by the intrinsic characteristics of β cells, are thought to be important for insulin effects; however, the underlying mechanism of such dynamics has not been fully revealed [80, 81].

Bottom Line: Encapsulation of pancreatic islets has been proposed and investigated for over three decades to improve islet transplantation outcomes and to eliminate the side effects of immunosuppressive medications.Of the numerous encapsulation systems developed in the past, microencapsulation have been studied most extensively so far.A wide variety of materials has been tested for microencapsulation in various animal models (including nonhuman primates or NHPs) and some materials were shown to induce immunoprotection to islet grafts without the need for chronic immunosuppression.

View Article: PubMed Central - PubMed

Affiliation: Division of Transplantation/Department of Surgery, University of Illinois at Chicago, IL 60612, USA ; Department of Diabetes and Metabolic Diseases Research, Beckman Research Institute of the City of Hope, 1500 E. Duarte Road, Duarte, CA 91010, USA.

ABSTRACT
Encapsulation of pancreatic islets has been proposed and investigated for over three decades to improve islet transplantation outcomes and to eliminate the side effects of immunosuppressive medications. Of the numerous encapsulation systems developed in the past, microencapsulation have been studied most extensively so far. A wide variety of materials has been tested for microencapsulation in various animal models (including nonhuman primates or NHPs) and some materials were shown to induce immunoprotection to islet grafts without the need for chronic immunosuppression. Despite the initial success of microcapsules in NHP models, the combined use of islet transplantation (allograft) and microencapsulation has not yet been successful in clinical trials. This review consists of three sections: introduction to islet transplantation, transplantation of encapsulated pancreatic islets as a treatment for patients with type 1 diabetes mellitus (T1DM), and present challenges and future perspectives.

No MeSH data available.


Related in: MedlinePlus