Glucagon-like peptide 1 undergoes differential tissue-specific metabolism in the anesthetized pig

1996 ◽  
Vol 271 (3) ◽  
pp. E458-E464 ◽  
Author(s):  
C. F. Deacon ◽  
L. Pridal ◽  
L. Klarskov ◽  
M. Olesen ◽  
J. J. Holst
Keyword(s):  
Immunosorbent Assay ◽  
Half Life ◽  
Biologically Active ◽  
Enzyme Linked Immunosorbent Assay ◽  
Metabolic Clearance ◽  
Tissue Specific ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Plasma Half Life ◽  
Differential Tissue

Glucagon-like peptide 1 (GLP-1) metabolism was studied in halothane-anesthetized pigs (n = 7) using processing-independent (PI) and COOH-terminal (C) radioimmunoassays (RIA) and an enzyme-linked immunosorbent assay (ELISA) specific for biologically active GLP-1. Renal extraction of endogenous GLP-1 was detected by PI-RIA (33.1 +/- 13.3%) and C-RIA (16.0 +/- 6.3%) and by all assays during GLP-1 infusion (ELISA, 69.4 +/- 6.3%; PI-RIA, 32.6 +/- 7.3%; C-RIA, 43.7 +/- 3.4%), indicating substantial fragmentation. Hepatic and pulmonary degradation were undetectable under basal conditions, but exogenous GLP-1 elimination by the liver (43.6 +/- 8.9%) and lungs (10.1 +/- 3.2%) was measured by ELISA, suggesting primarily NH2-terminal degradation. Endogenous GLP-1 extraction by the hindleg was only detected by C-RIA (16.0 +/- 6.3%). During GLP-1 infusion, greater hindleg extraction was measured by ELISA (38.5 +/- 6.8%) and C-RIA (33.0 +/- 6.4%) than by PI-RIA (11.4 +/- 3.2%), indicating limited degradation at each terminus or more substantial COOH-terminal degradation. A shorter (P < 0.01) plasma half-life was revealed by ELISA (1.5 +/- 0.4 min) than by PI-RIA (4.5 +/- 0.6 min) or C-RIA (4.1 +/- 0.5 min). Metabolic clearance rates measured by PI-RIA (20.0 +/- 3.8 ml.min-1.kg-1) and C-RIA (15.5 +/- 1.6 ml.min-1.kg-1) were shorter (P < 0.01) than that measured by ELISA (106.8 +/- 14.7 ml.min-1.kg-1). Tissue-specific differential metabolism of GLP-1 occurs, and NH2-terminal degradation, rendering GLP-1 inactive, is particularly important in its clearance.

Comparative metabolic clearance rate, volume of distribution and plasma half-life of human β-lipotropin and acth

Life Sciences ◽  
1978 ◽  
Vol 23 (23) ◽  
pp. 2323-2330 ◽  
Author(s):  
Anthony S. Liotta ◽  
Choh Hao Li ◽  
George C. Schussler ◽  
Dorothy T. Krieger
Keyword(s):  
Clearance Rate ◽  
Half Life ◽  
Volume Of Distribution ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Half Life

Formation of cyclic structure at amino-terminus of glucagon-like peptide-1 exhibited a prolonged half-life in vivo

2012 ◽  
Vol 96 (3) ◽  
pp. 362-370 ◽  
Author(s):  
Zhenghong Cao ◽  
Ying Li ◽  
Lida Tang ◽  
Weiren Xu ◽  
Changxiao Liu ◽  
...  
Keyword(s):  
Half Life ◽  
Amino Terminus ◽  
Cyclic Structure ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Construction and Expression of Recombinant Streptolysin-O and Preevaluation of Its Use in Immunoassays

2005 ◽  
Vol 12 (5) ◽  
pp. 683-684 ◽  
Author(s):  
Blanca Velázquez ◽  
Hugo Massaldi ◽  
Julio Battistoni ◽  
José A. Chabalgoity
Keyword(s):  
Immunosorbent Assay ◽  
Biologically Active ◽  
Enzyme Linked Immunosorbent Assay ◽  
Purification Process ◽  
Commercial Test ◽  
Streptolysin O ◽  
Complex Process

ABSTRACT Commercially available immunoassays for assessment of anti-streptolysin-O antibodies use native streptolysin-O obtained by a complex process. We prepared a biologically active recombinant streptolysin-O with higher yield and a simpler purification process. An enzyme-linked immunosorbent assay developed with this recombinant showed good correlation with a commercial test, suggesting that it could be suitable for immunoassays.

scholarly journals Pharmacokinetic Study of SKL-18287, a Novel Long-Acting Glucagon-Like Peptide-1 Receptor Agonist, in Rats, Monkeys and Mini-Pigs

Drug Research ◽  
2019 ◽  
Vol 69 (09) ◽  
pp. 479-486
Author(s):  
Mitsuaki Takeuchi ◽  
Masayuki Okamoto ◽  
Miyuki Tamura ◽  
Takayo Murase ◽  
Nobuhide Watanabe
Keyword(s):  
Half Life ◽  
Animal Species ◽  
Subcutaneous Administration ◽  
The United States ◽  
Pharmacokinetic Parameters ◽  
Target Tissue ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Mini Pigs

Abstract Background Long-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for treatment of type 2 diabetes (T2DM) in the United States, the European Union, and Japan. In our previous work, we designed and characterized a novel GLP-1 RA, SKL-18287. This RA consists of only natural L-amino acids, and is believed to exist in an oligomer form in systemic circulation. This unique feature may allow high biological stability and a long-lasting glucose lowering effect in T2DM treatment. In the present study, we investigated the pharmacokinetic properties of SKL-18287 in rats, monkeys, and mini-pigs. Tissue distributions of radioactivity were also studied in rats after subcutaneous administration of [3H]-SKL-18287. Methods Plasma concentrations of SKL-18287 were measured by LC-MS/MS after intravenous and subcutaneous administration of SKL-18287 in rats, monkeys, and mini-pigs. Pharmacokinetic parameters were then calculated and compared among these animal species. Tissue concentrations of radioactivity were determined by liquid scintillation counting following sample combustion, after subcutaneous administration of [3H]-SKL-18287 to rats. Results SKL-18287 showed an extended half-life of over 5 h, with good subcutaneous bioavailability, in all animal species. Prediction of the pharmacokinetic profiles of SKL-18287 in humans using an animal scale-up approach revealed an SKL-18287 half-life of 14.8 h. The radioactivity concentration in the pancreas, a target tissue of GLP-1RA, was relatively higher than in other tissues, until 12 h after [3H]-SKL-18287 administration. Conclusion SKL-18287 might be sufficient to maintain an effective concentration for a once-daily treatment for T2DM, and is a unique GLP-1 RA with a pancreas-selective feature.

scholarly journals A Short Half-Life αIIbβ3 Antagonist ANTP266 Reduces Thrombus Formation

2018 ◽  
Vol 19 (8) ◽  
pp. 2306 ◽  
Author(s):  
Tong-Dan Liu ◽  
Shen-Hong Ren ◽  
Xue Ding ◽  
Zhou-Ling Xie ◽  
Yi Kong
Keyword(s):  
Half Life ◽  
Bleeding Time ◽  
Thrombus Formation ◽  
Bleeding Risk ◽  
Effective Dosage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Severe Bleeding ◽  
Antithrombotic Agent ◽  
Integrin Αiibβ3 ◽  
Plasma Half Life

Integrin αIIbβ3 plays a pivotal role in platelet aggregation. Three αIIbβ3 antagonists have been approved by the Food and Drug Administration (FDA) for the treatment of cardiovascular diseases. Unfortunately, all of these three drugs can cause the side effect of severe bleeding. Therefore, developing a new αIIbβ3 antagonist with low bleeding was needed. In the present study, we screened compounds by using a fibrinogen/integrin αIIbβ3 enzyme-linked immunosorbent assay (ELISA), and a novel αIIbβ3 antagonist ANTP266 was attained. The antithrombotic effects of ANTP266 were estimated by using two animal models, the bleeding risk was estimated by using a mice tail cutting assay, and the plasma half-life time was tested by LC-MS/MS. The results showed that ANTP266 potently decreased thrombosis formation, while not prolonging bleeding time at its effective dosage. The bleeding of ANTP266 reduced rapidly as time went on from 5 to 60 min, but tirofiban produced high bleeding continuously. The plasma half-life of ANTP266 in rats was 10.8 min. Taken together, ANTP266 is an effective antithrombotic agent with a low bleeding risk. The shorter bleeding time benefits from its short plasma half-life. ANTP266 could be a candidate for developing the αIIbβ3 antagonist of rapid elimination for a patient undergoing percutaneous coronary intervention.

scholarly journals Anosmia and dysgeusia among COVID-19 patients are associated with low levels of serum Glucagon-like peptide 1 (GLP-1)

2021 ◽  
Author(s):  
Eli Ben-Chetrit ◽  
Ami Ben Yaa'cov ◽  
Ahamad Quiteineh ◽  
Ohad Atia ◽  
Eran Regev ◽  
...  
Keyword(s):  
Nasal Congestion ◽  
Serum Levels ◽  
Study Groups ◽  
Underlying Mechanism ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Lower Serum ◽  
Glucagon Like Peptide ◽  
Low Levels ◽  
Glucagon Like Peptide 1

Purpose: Anosmia and dysgeusia (AD) are common among COVID-19 patients. These symptoms are not frequently associated with rhinorrhea or nasal congestion and the underlying mechanism is unclear. Previous reports suggested that Glucagon-like peptide-1 (GLP-1) signaling plays a role in the modulation of olfaction and geusia. We aimed to assess the correlation between GLP-1 and COVID-19-associated AD. Methods: Blood samples obtained from COVID-19 patients with and without AD were tested for serum GLP-1 levels using enzyme-linked immunosorbent assay (ELISA). A second control group comprised of COVID-19-negative volunteers. Results: Forty-nine subjects were included in the study. Nineteen were positive for COVID-19. Of the 19 patients, ten had AD and nine declined such complaints. Age and basic metabolic rate were similar among all study groups. Serum GLP-1 levels were significantly lower among patients with AD as compared with patients without AD and COVID-19-negative individuals (1820 pg/ml vs 3536 pg/ml vs 3014 pg/ml, respectively, p<0.02). Conclusion: COVID-19 patients who reported of AD had lower serum levels of GLP-1 as compared with those lacking AD symptoms and COVID-19-negative individuals. These results suggest that GLP-1 may be involved in the pathogenesis of AD. However, further larger scale studies should corroborate our findings

Peptide Half-Life Extension: Divalent, Small-Molecule Albumin Interactions Direct the Systemic Properties of Glucagon-Like Peptide 1 (GLP-1) Analogues

2017 ◽  
Vol 60 (17) ◽  
pp. 7434-7446 ◽  
Author(s):  
Esben M. Bech ◽  
Manuel C. Martos-Maldonado ◽  
Pernille Wismann ◽  
Kasper K. Sørensen ◽  
Søren Blok van Witteloostuijn ◽  
...  
Keyword(s):  
Small Molecule ◽  
Half Life ◽  
Life Extension ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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