Glucagon-like peptide 1 (GLP-1)

Molecular Metabolism, Journal Year: 2019, Volume and Issue: 30, P. 72 - 130

Published: Sept. 30, 2019

Background: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential.Among the numerous metabolic effects of GLP-1 are glucose-dependent stimulation insulin secretion, decrease gastric emptying, inhibition food intake, increase natriuresis and diuresis, modulation rodent b-cell proliferation.GLP-1 also has cardio-and neuroprotective effects, decreases inflammation apoptosis, implications for learning memory, reward behavior, palatability.Biochemically modified enhanced potency sustained action, receptor agonists successfully in clinical use treatment type-2 diabetes, several GLP-1-based pharmacotherapies evaluation obesity.Scope review: In this review, we provide detailed overview on nature its pharmacology discuss therapeutic various diseases.Major conclusions: Since discovery, emerged as pleiotropic myriad functions that go well beyond classical identification an incretin hormone.The beneficial render interesting candidate development to treat obesity, neurodegenerative disorders

Language: Английский

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Pharmacology, Physiology, and Mechanisms of Incretin Hormone Action

Cell Metabolism, Journal Year: 2013, Volume and Issue: 17(6), P. 819 - 837

Published: May 16, 2013

Language: Английский

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Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1

Cell Metabolism, Journal Year: 2018, Volume and Issue: 27(4), P. 740 - 756

Published: April 1, 2018

Language: Английский

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GLP-1 Receptor Localization in Monkey and Human Tissue: Novel Distribution Revealed With Extensively Validated Monoclonal Antibody

Endocrinology, Journal Year: 2014, Volume and Issue: 155(4), P. 1280 - 1290

Published: Jan. 27, 2014

Glucagon-like peptide 1 (GLP-1) analogs are increasingly being used in the treatment of type 2 diabetes. It is clear that these drugs lower blood glucose through an increase insulin secretion and a lowering glucagon secretion; addition, they body weight systolic pressure heart rate. Using new monoclonal antibody for immunohistochemistry, we detected GLP-1 receptor (GLP-1R) important target organs humans monkeys. In pancreas, GLP-1R was predominantly localized β-cells with markedly weaker expression acinar cells. Pancreatic ductal epithelial cells did not express GLP-1R. kidney lung, exclusively expressed smooth muscle walls arteries arterioles. heart, myocytes sinoatrial node. gastrointestinal tract, highest seen Brunner's gland duodenum, level parietal muscularis externa stomach myenteric plexus neurons throughout gut. No primate liver thyroid. immunohistochemistry confirmed by functional using situ ligand binding (125)I-GLP-1. conclusion, results give insight into molecular mode action identifying exact cellular localization

Language: Английский

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The Discovery and Development of Liraglutide and Semaglutide

Frontiers in Endocrinology, Journal Year: 2019, Volume and Issue: 10

Published: April 12, 2019

The discovery of glucagon-like peptide-1 (GLP-1), an incretin hormone with important effects on glycemic control and body weight regulation, led to efforts extend its half-life make it therapeutically effective in people type 2 diabetes (T2D). development short- then long-acting GLP-1 receptor agonists (GLP-1RAs) followed. Our article charts the analogs liraglutide and, subsequently, semaglutide. We examine chemistry employed designing semaglutide, human nonhuman studies used investigate their cellular targets pharmacological effects, ongoing investigations into new applications formulations these drugs. Reversible binding albumin was for systemic protraction optimal fatty acid linker combinations identified maximize while maintaining (GLP-1R) potency. GLP-1RAs mediate via this receptor, which is expressed pancreas, gastrointestinal tract, heart, lungs, kidneys brain. GLP-1Rs pancreas brain have been shown account respective improvements that are evident Both semaglutide also positively affect cardiovascular (CV) outcomes individuals T2D, although precise mechanism still being explored. Significant loss, through effect reduce energy intake, approval (3.0 mg) treatment obesity, indication currently under investigation Other include nonalcoholic liver disease (NASH) use oral formulation T2D. In summary, rational design has two analogs, made a vast contribution management T2D terms control, weight, blood pressure, lipids, beta-cell function CV outcomes. Furthermore, may provide additional benefits relation adherence. addition obesity NASH.

Language: Английский

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A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents

Nature Medicine, Journal Year: 2014, Volume and Issue: 21(1), P. 27 - 36

Published: Dec. 8, 2014

Language: Английский

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Pharmacology, Physiology, and Mechanisms of Action of Dipeptidyl Peptidase-4 Inhibitors

Endocrine Reviews, Journal Year: 2014, Volume and Issue: 35(6), P. 992 - 1019

Published: Sept. 12, 2014

Dipeptidyl peptidase-4 (DPP4) is a widely expressed enzyme transducing actions through an anchored transmembrane molecule and soluble circulating protein. Both membrane-associated DPP4 exert catalytic activity, cleaving proteins containing position 2 alanine or proline. DPP4-mediated enzymatic cleavage alternatively inactivates peptides generates new bioactive moieties that may competing novel activities. The widespread use of selective inhibitors for the treatment type diabetes has heightened interest in molecular mechanisms which their pleiotropic actions. Here we review biology with focus on: 1) identification pharmacological vs physiological substrates; 2) elucidation studies employing genetic elimination chemical reduction activity. We data identifying roles key substrates glucoregulatory, anti-inflammatory, cardiometabolic both preclinical clinical studies. Finally, highlight experimental pitfalls technical challenges encountered designed to understand action downstream targets activated by inhibition DPP4.

Language: Английский

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The Cardiovascular Biology of Glucagon-like Peptide-1

Cell Metabolism, Journal Year: 2016, Volume and Issue: 24(1), P. 15 - 30

Published: June 25, 2016

Language: Английский

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GLP-1 receptor activation and Epac2 link atrial natriuretic peptide secretion to control of blood pressure

Nature Medicine, Journal Year: 2013, Volume and Issue: 19(5), P. 567 - 575

Published: March 31, 2013

Language: Английский

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Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease

Physiological Reviews, Journal Year: 2015, Volume and Issue: 95(2), P. 513 - 548

Published: April 1, 2015

The preproglucagon gene ( Gcg) is expressed by specific enteroendocrine cells (L-cells) of the intestinal mucosa, pancreatic islet α-cells, and a discrete set neurons within nucleus solitary tract. Gcg encodes multiple peptides including glucagon, glucagon-like peptide-1, peptide-2, oxyntomodulin, glicentin. Of these, glucagon GLP-1 have received most attention because important roles in glucose metabolism, involvement diabetes other disorders, application to therapeutics. generally accepted model that improves homeostasis indirectly via stimulation nutrient-induced insulin release reducing secretion. Yet body literature surrounding physiology reveals an incompletely understood complex system includes peripheral central actions regulate energy homeostasis. On hand, established principally as counterregulatory hormone, increasing response physiological challenges threaten adequate blood levels driving production restore euglycemia. However, there also exists potential role for regulating expenditure has recently been suggested pharmacological studies. It becoming apparent cross-talk between proglucagon derived-peptides, e.g., inhibits secretion, some additive or synergistic interaction dual glucagon/GLP-1 agonists cause more weight loss than single agonists. In this review, we discuss functions both comparing contrasting how these function, variably concert opposition,

Language: Английский

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