Metabolic clearance rates of oxyntomodulin and glucagon in the rat: contribution of the kidney

Kervran, A.; Dubrasquet, M; Blache, Philippe; Martinez, Jean; Bataille, D.

doi:10.1016/0167-0115(90)90194-2

Cited by 47 publications

(46 citation statements)

References 26 publications

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“…Vessel cannulation in animals has been the cornerstone for performing PK experiments and is the standard practice in drug discovery as it has been shown to provide accurate and reliable results [12][13][14][15][16][17]. PK experiments involve administering the drug compound and taking blood samples in order to assess the biological effect.…”

Section: Ra-cusum Analysis For Jugular Vein Cannulationmentioning

confidence: 99%

“…In this study we evaluated the learning curve for cannulating the femoral and the external jugular vein, two of the most commonly used i.v. accesses (other including the saphenous vein and the carotid artery) [12,13,17,25].…”

Section: Ra-cusum Analysis For Jugular Vein Cannulationmentioning

confidence: 99%

“…The cannulation of these vessels was used in an animal model developed in-house in order to evaluate the pharmacokinetic properties (PK) of peptides developed as part of a drug discovery anti-obesity program. The use of animals for such PK experiments is standard practice and provides accurate and reliable results [12][13][14][15][16][17]. Optimal and timely vessel cannulation is important for this protocol; time is a critical component when performing PK experiments as there are limitations to time animals can remain under anaesthesia.…”

Section: Introductionmentioning

confidence: 99%

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Learning curve of vessel cannulation in rats using cumulative sum analysis

Christakis

Georgiou

Minnion

et al. 2015

Journal of Surgical Research

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Extensive experience in rodent surgery and training junior surgeons Cover LetterDear Ms/Mr, We would be grateful if you would consider our manuscript entitled "Learning curve of cannulation of jugular and femoral vein in rats using Cumulative Summation Analysis" for publication in The Journal of Surgical Research. Our study investigates the learning curve required for competency and proficiency at blood vessel cannulation in rodents.Vessel cannulation in rats, such as of the femoral and jugular vein, is a technically challenging procedure even for an experienced surgeon. In this study we analyse the results of 200 cannulations of the femoral and jugular vein in rats performed within one year by a single surgeon. The use of Cumulative Summation analysis allows calculating the required experience to most effectively cannulate the jugular and femoral vein, which is approximately 50 and 100 cases, respectively.These results highlight the difficulty involved in performing such micro-surgical operations in rodents. The knowledge of the average time taken to cannulate these vessels allows experiments to be optimally planned, avoiding unexpected time over-runs. Furthermore, our results bring into the spotlight the need for training and direct supervision for the inexperienced researchers, as there is an ongoing need to reduce animal use in research through minimising adverse events.To the authors' knowledge this is the first study to report the learning curve for mastering the technique of catheterisation of the femoral and jugular vein in rats. We feel it will be of interest to readers of The Journal of Surgical Research, and particularly those using rodent microsurgery. Subject category: ResearchAuthors' contributions I.C., J.C., R.S. carried out the design and coordinated the study, participated in all of the experiments and prepared the manuscript. J.M., P.G., V.C., F.P., K.M., S.B.provided assistance in the design of the study, coordinated and carried out most of the experiments and participated in manuscript preparation. T.T., F.P., K.M. and S.B.approved the final version of the manuscript. All authors have read and approved the content of the manuscript.-3 - AbstractBackground:

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Section: Ra-cusum Analysis For Jugular Vein Cannulationmentioning

confidence: 99%

Section: Ra-cusum Analysis For Jugular Vein Cannulationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Learning curve of vessel cannulation in rats using cumulative sum analysis

Christakis

Georgiou

Minnion

et al. 2015

Journal of Surgical Research

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“…injected OXM in mice, to determine a injection paradigm, which would mimic the natural OXM release after food uptake. OXM is characterized by its short halflife of 6.4 +/-0.5 min due to rapid DPP-4 degradation [232,259]. Instead of being refed mice received an injection, leading to a final blood concentration of ~465 nM at ZT1 after 12 h of fasting.…”

Section: Oxyntomodulin Secretion Is Postprandially Inducedmentioning

confidence: 99%

Metabolic Synchronization of the Liver Circadian Clock

Landgraf¹

2011

The Endocrine Society's 93rd Annual Meeting &Amp; Expo, June 4–7, 2011 - Boston

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“…It has been shown that renal clearance accounts for 35% of the peptide disappearance from the plasma after OXM administration in rats. 14 In vitro protease degradation assays suggest that OXM may be susceptible to proteolysis by dipeptidyl peptidase IV (DPP-IV) 15 and neutral endopeptidase 24.11 (NEP). 16,17 To overcome the factors limiting OXM as a potential anti-obesity therapy, we have recently investigated the structure-function relationships and the degradation pathways of OXM, and identified the parts of the OXM sequence that are sensitive to degradation and/or involved in the binding to the glucagon-like peptide-1 (GLP-1) receptor.…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous oxyntomodulin analogue administration reduces body weight in lean and obese rodents

et al. 2010

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Objective: To determine the efficacy of a long-acting oxyntomodulin (OXM) analogue, OXM6421, in inhibiting food intake and decreasing body weight in lean and diet-induced obese (DIO) rodents. Research design and methods: The glucagon-like peptide-1 (GLP-1) receptor binding affinity and efficacy, sensitivity to enzymatic degradation in vitro and persistence in the circulation after peripheral administration were investigated for OXM6421 and compared with native OXM. The chronic effect of OXM6421 on food intake, body weight and energy expenditure was examined in lean rats, and its anti-obesity potential was evaluated in DIO mice. Results: OXM6421 showed enhanced GLP-1 receptor binding affinity and cyclic adenosine monophosphate (cAMP) stimulation, and higher resistance to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase (NEP) compared with native OXM. OXM6421 persisted longer in the circulation than OXM after peripheral administration. Acute administration of OXM6421 potently inhibited food intake in lean rodents, with cumulative effects lasting up to 24 h. In lean rats, daily subcutaneous (s.c.) administration of OXM6421 caused greater weight loss than the pair-fed animals, and a higher rate of oxygen consumption than both the pair-fed and the saline controls. In DIO mice, continuous s.c. infusion of OXM6421 resulted in a significant weight loss, accompanied by an improvement in glucose homeostasis and an increase in circulating adiponectin levels. Once-daily s.c. administration of OXM6421 for 21 days caused sustained weight loss in DIO mice. Conclusion: OXM6421 induces negative energy balance in both lean and obese rodents, suggesting that long-acting OXM analogues may represent a potential therapy for obesity.

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Metabolic clearance rates of oxyntomodulin and glucagon in the rat: contribution of the kidney

Cited by 47 publications

References 26 publications

Learning curve of vessel cannulation in rats using cumulative sum analysis

Learning curve of vessel cannulation in rats using cumulative sum analysis

Metabolic Synchronization of the Liver Circadian Clock

Subcutaneous oxyntomodulin analogue administration reduces body weight in lean and obese rodents

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