Therapeutic strategies based on glucagon-like peptide 1.

Carolyn F Deacon

Therapeutic strategies based on glucagon-like peptide 1.

Carolyn F Deacon

Biomedicinsk Institut

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

299 Citationer (Scopus)

Abstract

Udgivelsesdato: 2004-Sep

Originalsprog	Engelsk
Tidsskrift	Diabetes
Vol/bind	53
Udgave nummer	9
Sider (fra-til)	2181-9
Antal sider	8
ISSN	0012-1797
Status	Udgivet - 2004

Bibliografisk note

Keywords: Amino Acid Sequence; Antigens, CD26; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Humans; Molecular Sequence Data; Peptide Fragments; Protein Precursors

Citationsformater

@article{fa4b7910ab4b11ddb5e9000ea68e967b,

title = "Therapeutic strategies based on glucagon-like peptide 1.",

abstract = "Glucagon-like peptide (GLP)-1 is an incretin hormone with potent glucose-dependent insulinotropic and glucagonostatic actions, trophic effects on the pancreatic beta-cells, and inhibitory effects on gastrointestinal secretion and motility, which combine to lower plasma glucose and reduce glycemic excursions. Furthermore, via its ability to enhance satiety, GLP-1 reduces food intake, thereby limiting weight gain, and may even cause weight loss. Taken together, these actions give GLP-1 a unique profile, considered highly desirable for an antidiabetic agent, particularly since the glucose dependency of its antihyperglycemic effects should minimize any risk of severe hypoglycemia. However, its pharmacokinetic/pharmacodynamic profile is such that native GLP-1 is not therapeutically useful. Thus, while GLP-1 is most effective when administered continuously, single subcutaneous injections have short-lasting effects. GLP-1 is highly susceptible to enzymatic degradation in vivo, and cleavage by dipeptidyl peptidase IV (DPP-IV) is probably the most relevant, since this occurs rapidly and generates a noninsulinotropic metabolite. Strategies for harnessing GLP-1's therapeutic potential, based on an understanding of factors influencing its metabolic stability and pharmacokinetic/pharmacodynamic profile, have therefore been the focus of intense research in both academia and the pharmaceutical industry. Such strategies include DPP-IV-resistant GLP-1 analogs and selective enzyme inhibitors to prevent in vivo degradation of the peptide.",

author = "Deacon, {Carolyn F}",

note = "Keywords: Amino Acid Sequence; Antigens, CD26; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Humans; Molecular Sequence Data; Peptide Fragments; Protein Precursors",

year = "2004",

language = "English",

volume = "53",

pages = "2181--9",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "9",

}

TY - JOUR

T1 - Therapeutic strategies based on glucagon-like peptide 1.

AU - Deacon, Carolyn F

N1 - Keywords: Amino Acid Sequence; Antigens, CD26; Diabetes Mellitus, Type 2; Glucagon; Glucagon-Like Peptide 1; Humans; Molecular Sequence Data; Peptide Fragments; Protein Precursors

PY - 2004

Y1 - 2004

N2 - Glucagon-like peptide (GLP)-1 is an incretin hormone with potent glucose-dependent insulinotropic and glucagonostatic actions, trophic effects on the pancreatic beta-cells, and inhibitory effects on gastrointestinal secretion and motility, which combine to lower plasma glucose and reduce glycemic excursions. Furthermore, via its ability to enhance satiety, GLP-1 reduces food intake, thereby limiting weight gain, and may even cause weight loss. Taken together, these actions give GLP-1 a unique profile, considered highly desirable for an antidiabetic agent, particularly since the glucose dependency of its antihyperglycemic effects should minimize any risk of severe hypoglycemia. However, its pharmacokinetic/pharmacodynamic profile is such that native GLP-1 is not therapeutically useful. Thus, while GLP-1 is most effective when administered continuously, single subcutaneous injections have short-lasting effects. GLP-1 is highly susceptible to enzymatic degradation in vivo, and cleavage by dipeptidyl peptidase IV (DPP-IV) is probably the most relevant, since this occurs rapidly and generates a noninsulinotropic metabolite. Strategies for harnessing GLP-1's therapeutic potential, based on an understanding of factors influencing its metabolic stability and pharmacokinetic/pharmacodynamic profile, have therefore been the focus of intense research in both academia and the pharmaceutical industry. Such strategies include DPP-IV-resistant GLP-1 analogs and selective enzyme inhibitors to prevent in vivo degradation of the peptide.

AB - Glucagon-like peptide (GLP)-1 is an incretin hormone with potent glucose-dependent insulinotropic and glucagonostatic actions, trophic effects on the pancreatic beta-cells, and inhibitory effects on gastrointestinal secretion and motility, which combine to lower plasma glucose and reduce glycemic excursions. Furthermore, via its ability to enhance satiety, GLP-1 reduces food intake, thereby limiting weight gain, and may even cause weight loss. Taken together, these actions give GLP-1 a unique profile, considered highly desirable for an antidiabetic agent, particularly since the glucose dependency of its antihyperglycemic effects should minimize any risk of severe hypoglycemia. However, its pharmacokinetic/pharmacodynamic profile is such that native GLP-1 is not therapeutically useful. Thus, while GLP-1 is most effective when administered continuously, single subcutaneous injections have short-lasting effects. GLP-1 is highly susceptible to enzymatic degradation in vivo, and cleavage by dipeptidyl peptidase IV (DPP-IV) is probably the most relevant, since this occurs rapidly and generates a noninsulinotropic metabolite. Strategies for harnessing GLP-1's therapeutic potential, based on an understanding of factors influencing its metabolic stability and pharmacokinetic/pharmacodynamic profile, have therefore been the focus of intense research in both academia and the pharmaceutical industry. Such strategies include DPP-IV-resistant GLP-1 analogs and selective enzyme inhibitors to prevent in vivo degradation of the peptide.

M3 - Journal article

C2 - 15331525

SN - 0012-1797

VL - 53

SP - 2181

EP - 2189

JO - Diabetes

JF - Diabetes

IS - 9

ER -