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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

Amino acid sequence of GLP-1 and exendin-4. GLP-1 consists of two active circulating forms, GLP-1 (7–36) amide and GLP-1 (7–37).
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Related In: Results  -  Collection


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fig1: Amino acid sequence of GLP-1 and exendin-4. GLP-1 consists of two active circulating forms, GLP-1 (7–36) amide and GLP-1 (7–37).

Mentions: The biological function of GLP-1 is well known as an incretin hormone released from gastrointestinal L-cells [1, 3]. Native GLP-1 (1–37) is produced two active circulating forms, GLP-1 (7–37) and GLP-1 (7–36) amide [6] (Figure 1). GLP-1 (7–36) amide is more abundant in blood. Incretin effect of GLP-1 is reviewed in several papers [2, 3, 6]. Intact GLP-1 promotes insulin secretion, inhibits glucagon secretion in pancreas, and increases the synthesis of proinsulin. Furthermore, GLP-1 promotes proliferation of pancreatic islet β-cell, inhibits β-cell apoptosis, delays in gastric emptying, and induces weight loss by suppression of appetite in type 2 diabetes [2, 5]. GLP-1, also, enhances the hepatic glucose uptake due to increasing glycogen syntheses activity [8]. Although GLP-1 has many advantages, however, its application in clinical trials is considerably restricted because GLP-1 is degraded rapidly by dipeptidyl-peptidase (DPP-IV), along with renal clearance [9]. Accordingly, long-acting GLP-1 receptor agonists such as exendin-4, which are more resistant to degradation by DPP-IV, may have a long term therapeutic efficacy compared with GLP-1 [2].


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

Kim PH, Kim SW - ISRN Endocrinol (2012)

Amino acid sequence of GLP-1 and exendin-4. GLP-1 consists of two active circulating forms, GLP-1 (7–36) amide and GLP-1 (7–37).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Amino acid sequence of GLP-1 and exendin-4. GLP-1 consists of two active circulating forms, GLP-1 (7–36) amide and GLP-1 (7–37).
Mentions: The biological function of GLP-1 is well known as an incretin hormone released from gastrointestinal L-cells [1, 3]. Native GLP-1 (1–37) is produced two active circulating forms, GLP-1 (7–37) and GLP-1 (7–36) amide [6] (Figure 1). GLP-1 (7–36) amide is more abundant in blood. Incretin effect of GLP-1 is reviewed in several papers [2, 3, 6]. Intact GLP-1 promotes insulin secretion, inhibits glucagon secretion in pancreas, and increases the synthesis of proinsulin. Furthermore, GLP-1 promotes proliferation of pancreatic islet β-cell, inhibits β-cell apoptosis, delays in gastric emptying, and induces weight loss by suppression of appetite in type 2 diabetes [2, 5]. GLP-1, also, enhances the hepatic glucose uptake due to increasing glycogen syntheses activity [8]. Although GLP-1 has many advantages, however, its application in clinical trials is considerably restricted because GLP-1 is degraded rapidly by dipeptidyl-peptidase (DPP-IV), along with renal clearance [9]. Accordingly, long-acting GLP-1 receptor agonists such as exendin-4, which are more resistant to degradation by DPP-IV, may have a long term therapeutic efficacy compared with GLP-1 [2].

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