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Polymer-based delivery of glucagon-like Peptide-1 for the treatment of diabetes.

Kim PH, Kim SW - ISRN Endocrinol (2012)

Bottom Line: Herein, we discuss the modification of the expression cassettes and peptides for long-term production and secretion of the native peptides.In addition, the characteristics of nonviral or viral system used for a delivery of a modified GLP-1 or exendin-4 are described.Furthermore, recent efforts to improve the biological half-life of GLP-1 or exendin-4 peptide via chemical conjugation with various smart polymers via chemical conjugation compared with native peptide are discussed.

View Article: PubMed Central - PubMed

Affiliation: Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.

ABSTRACT
The incretin hormones, glucagon-like peptide-1 (GLP-1) and its receptor agonist (exendin-4), are well known for glucose homeostasis, insulinotropic effect, and effects on weight loss and food intake. However, due to the rapid degradation of GLP-1 by dipeptidylpeptidase-IV (DPP-IV) enzyme and renal elimination of exendin-4, their clinical applications have been restricted. Although exendin-4 has longer half-life than GLP-1, it still requires frequent injections to maintain efficacy for the treatment of diabetes. In recent decades, various polymeric delivery systems have been developed for the delivery of GLP-1 and exendin-4 genes or peptides for their long-term action and the extra production in ectopic tissues. Herein, we discuss the modification of the expression cassettes and peptides for long-term production and secretion of the native peptides. In addition, the characteristics of nonviral or viral system used for a delivery of a modified GLP-1 or exendin-4 are described. Furthermore, recent efforts to improve the biological half-life of GLP-1 or exendin-4 peptide via chemical conjugation with various smart polymers via chemical conjugation compared with native peptide are discussed.

No MeSH data available.


Related in: MedlinePlus

Potentiation therapy based on incretin for the treatment of diabetes.
© Copyright Policy - open-access
Related In: Results  -  Collection


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fig2: Potentiation therapy based on incretin for the treatment of diabetes.

Mentions: At this point, more investigations remained to be explored. For example, it is that activator, inhibitor, or siRNA capable of activation or inactivation of action mechanism of GLP-1 and its receptor or target of another kind of receptor such as GLP-2 receptor. At the same time, the sensitivity of these treatments to patients has to be considered for personalized diagnosis and therapy due to the difference against GLP-1 receptor responsiveness and sensitivity in each person. Finally, diabetic treatment will need combination therapy with other existing treatment to induce an increase of both endogenous and exogenous incretin hormones for sufficient therapeutic efficacies (Figure 2). In this sense, polymeric-based on incretin approaches may serve as intriguing tools to generate more therapeutic GLP-1 or exendin-4 for diabetes. With all these efforts, therapeutic applications of incretin will be realized as the positive impact with little side-effects in a near future.


Polymer-based delivery of glucagon-like Peptide-1 for the treatment of diabetes.

Kim PH, Kim SW - ISRN Endocrinol (2012)

Potentiation therapy based on incretin for the treatment of diabetes.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369441&req=5

fig2: Potentiation therapy based on incretin for the treatment of diabetes.
Mentions: At this point, more investigations remained to be explored. For example, it is that activator, inhibitor, or siRNA capable of activation or inactivation of action mechanism of GLP-1 and its receptor or target of another kind of receptor such as GLP-2 receptor. At the same time, the sensitivity of these treatments to patients has to be considered for personalized diagnosis and therapy due to the difference against GLP-1 receptor responsiveness and sensitivity in each person. Finally, diabetic treatment will need combination therapy with other existing treatment to induce an increase of both endogenous and exogenous incretin hormones for sufficient therapeutic efficacies (Figure 2). In this sense, polymeric-based on incretin approaches may serve as intriguing tools to generate more therapeutic GLP-1 or exendin-4 for diabetes. With all these efforts, therapeutic applications of incretin will be realized as the positive impact with little side-effects in a near future.

Bottom Line: Herein, we discuss the modification of the expression cassettes and peptides for long-term production and secretion of the native peptides.In addition, the characteristics of nonviral or viral system used for a delivery of a modified GLP-1 or exendin-4 are described.Furthermore, recent efforts to improve the biological half-life of GLP-1 or exendin-4 peptide via chemical conjugation with various smart polymers via chemical conjugation compared with native peptide are discussed.

View Article: PubMed Central - PubMed

Affiliation: Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.

ABSTRACT
The incretin hormones, glucagon-like peptide-1 (GLP-1) and its receptor agonist (exendin-4), are well known for glucose homeostasis, insulinotropic effect, and effects on weight loss and food intake. However, due to the rapid degradation of GLP-1 by dipeptidylpeptidase-IV (DPP-IV) enzyme and renal elimination of exendin-4, their clinical applications have been restricted. Although exendin-4 has longer half-life than GLP-1, it still requires frequent injections to maintain efficacy for the treatment of diabetes. In recent decades, various polymeric delivery systems have been developed for the delivery of GLP-1 and exendin-4 genes or peptides for their long-term action and the extra production in ectopic tissues. Herein, we discuss the modification of the expression cassettes and peptides for long-term production and secretion of the native peptides. In addition, the characteristics of nonviral or viral system used for a delivery of a modified GLP-1 or exendin-4 are described. Furthermore, recent efforts to improve the biological half-life of GLP-1 or exendin-4 peptide via chemical conjugation with various smart polymers via chemical conjugation compared with native peptide are discussed.

No MeSH data available.


Related in: MedlinePlus