Standard procedures for blood withdrawal in conscious male rats induce stress and profoundly affect glucose tolerance and secretion of glucoregulatory hormones
Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved..
OBJECTIVE: A fundamental difference between physiological and pharmacological studies in rats and humans is that withdrawal of blood from conscious rats necessitates restraint which inevitably inflicts a higher level of stress. We investigated the impact of handling on acute glucose regulation and secretion of glucoregulatory hormones in rats.
METHODS: Fasted male Sprague Dawley rats (375-400 g, n = 11) were given an oral glucose tolerance test (OGTT) by gavage (2 g/kg). Blood was sampled frequently until 90 min after challenge by handheld sampling (HS) or by automated sampling (AS). In the HS experiment, blood was withdrawn by restraint and sublingual vein puncture; two weeks later, samples were obtained by AS through an implanted catheter in a carotid artery, allowing sampling without disturbing the animals.
RESULTS: On the day of HS, post challenge glucose AUCs were ∼17% higher (P < 0.0001), despite gastric emptying (AUC) being reduced by ∼30% (P < 0.0001). Plasma insulin AUC was 3.5-fold lower (P < 0.001), and glucose-dependent insulinotropic peptide (GIP) AUC was reduced by ∼36% but glucagon-like peptide-1 concentrations were not affected. Glucagon concentrations were higher both before and after challenge (fold difference in AUCs = 3.3). Adrenocorticotropin (ACTH) and corticosterone AUCs were 2.4-fold and 3.6-fold higher (P < 0.001), respectively.
DISCUSSION AND CONCLUSION: Our study highlights that sampling of blood from conscious rats by sublingual vein puncture inflicts stress which reduces glucose absorption and glucose tolerance and blunts secretion of insulin and GIP. As blood sampling in humans are less stressful, standard procedures of conducting OGTT's in rats by HS presumably introduce an interspecies difference that may have negative consequences for translatability of test results.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:69 |
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| Enthalten in: |
Molecular metabolism - 69(2023) vom: 04. März, Seite 101689 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pedersen, Kent [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.03.2023 Date Revised 12.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.molmet.2023.101689 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Standard procedures for blood withdrawal in conscious male rats induce stress and profoundly affect glucose tolerance and secretion of glucoregulatory hormones |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved. | ||
| 520 | |a OBJECTIVE: A fundamental difference between physiological and pharmacological studies in rats and humans is that withdrawal of blood from conscious rats necessitates restraint which inevitably inflicts a higher level of stress. We investigated the impact of handling on acute glucose regulation and secretion of glucoregulatory hormones in rats | ||
| 520 | |a METHODS: Fasted male Sprague Dawley rats (375-400 g, n = 11) were given an oral glucose tolerance test (OGTT) by gavage (2 g/kg). Blood was sampled frequently until 90 min after challenge by handheld sampling (HS) or by automated sampling (AS). In the HS experiment, blood was withdrawn by restraint and sublingual vein puncture; two weeks later, samples were obtained by AS through an implanted catheter in a carotid artery, allowing sampling without disturbing the animals | ||
| 520 | |a RESULTS: On the day of HS, post challenge glucose AUCs were ∼17% higher (P < 0.0001), despite gastric emptying (AUC) being reduced by ∼30% (P < 0.0001). Plasma insulin AUC was 3.5-fold lower (P < 0.001), and glucose-dependent insulinotropic peptide (GIP) AUC was reduced by ∼36% but glucagon-like peptide-1 concentrations were not affected. Glucagon concentrations were higher both before and after challenge (fold difference in AUCs = 3.3). Adrenocorticotropin (ACTH) and corticosterone AUCs were 2.4-fold and 3.6-fold higher (P < 0.001), respectively | ||
| 520 | |a DISCUSSION AND CONCLUSION: Our study highlights that sampling of blood from conscious rats by sublingual vein puncture inflicts stress which reduces glucose absorption and glucose tolerance and blunts secretion of insulin and GIP. As blood sampling in humans are less stressful, standard procedures of conducting OGTT's in rats by HS presumably introduce an interspecies difference that may have negative consequences for translatability of test results | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Glucose intolerance | |
| 650 | 4 | |a Handheld blood sampling | |
| 650 | 4 | |a Incretin hormones | |
| 650 | 4 | |a Insulin secretion | |
| 650 | 4 | |a Rats | |
| 650 | 4 | |a Stress hormones | |
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| 700 | 1 | |a Fledelius, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Holst, Jens Juul |e verfasserin |4 aut | |
| 700 | 1 | |a Hjuler, Sara Toftegaard |e verfasserin |4 aut | |
| 700 | 1 | |a Kuhre, Rune Ehrenreich |e verfasserin |4 aut | |
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