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Glucagon clearance is regulated by nutritional state : Evidence from experimental studies in mice

Zhou, Alyssa ; Pacini, Giovanni ; Ahrén, Bo LU and D'Argenio, David Z. (2014) In Diabetologia 57(4). p.801-808
Abstract

Aims/hypothesis: Given the importance of glucagon in the development of type 2 diabetes and as a potential therapeutic agent, the aim of this study was to characterise glucagon kinetics in mice and its regulation by the nutritional state. Methods: Anaesthetised C57BL/6 mice fed normal or high-fat diets, or fasted, were injected intravenously with glucagon (0.1, 0.3, 1.0, 10.0 or 20 μg/kg); blood samples were withdrawn before injection and 1, 3, 5, 10, 20 min thereafter for glucagon assay by RIA. Glucagon kinetics were described by two-compartment models using a population analysis. Results: The population mean and between-animal SD of glucagon clearance in the fed mice was 6.03±2.58 ml/min, with a rapid elimination half-life of... (More)

Aims/hypothesis: Given the importance of glucagon in the development of type 2 diabetes and as a potential therapeutic agent, the aim of this study was to characterise glucagon kinetics in mice and its regulation by the nutritional state. Methods: Anaesthetised C57BL/6 mice fed normal or high-fat diets, or fasted, were injected intravenously with glucagon (0.1, 0.3, 1.0, 10.0 or 20 μg/kg); blood samples were withdrawn before injection and 1, 3, 5, 10, 20 min thereafter for glucagon assay by RIA. Glucagon kinetics were described by two-compartment models using a population analysis. Results: The population mean and between-animal SD of glucagon clearance in the fed mice was 6.03±2.58 ml/min, with a rapid elimination half-life of 2.92±1.21 min. Fasted mice showed a slower glucagon clearance. The kinetics of glucagon in the fed and fasted group was linear across this large dose range. The mice fed a high-fat diet, however, showed non-linear kinetics with a faster terminal clearance of 20.4±5.45 ml/min (p<0.001) and a shorter elimination half-life of 1.59±0.606 (p<0.001) min relative to normal mice. Conclusions/interpretation: This first systematic dose-ranging study of glucagon kinetics produced several findings: (1) a linear two-compartment model describes glucagon in normal C57BL/6 mice; (2) fasting reduces the clearance of glucagon and (3) high-fat diet enhances the clearance of glucagon. These results may direct future studies on glucagon physiology and indicate that there are other mechanisms, not included in the current model, needed to fully explain glucagon's kinetics.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glucagon clearance, Glucagon kinetics, Population analysis
in
Diabetologia
volume
57
issue
4
pages
8 pages
publisher
Springer
external identifiers
  • pmid:24370975
  • scopus:84896073844
ISSN
0012-186X
DOI
10.1007/s00125-013-3148-x
language
English
LU publication?
yes
id
f21942e9-4a36-4948-9f97-84e1ab7af714
date added to LUP
2018-10-01 12:55:37
date last changed
2020-05-26 04:56:01
@article{f21942e9-4a36-4948-9f97-84e1ab7af714,
  abstract     = {<p>Aims/hypothesis: Given the importance of glucagon in the development of type 2 diabetes and as a potential therapeutic agent, the aim of this study was to characterise glucagon kinetics in mice and its regulation by the nutritional state. Methods: Anaesthetised C57BL/6 mice fed normal or high-fat diets, or fasted, were injected intravenously with glucagon (0.1, 0.3, 1.0, 10.0 or 20 μg/kg); blood samples were withdrawn before injection and 1, 3, 5, 10, 20 min thereafter for glucagon assay by RIA. Glucagon kinetics were described by two-compartment models using a population analysis. Results: The population mean and between-animal SD of glucagon clearance in the fed mice was 6.03±2.58 ml/min, with a rapid elimination half-life of 2.92±1.21 min. Fasted mice showed a slower glucagon clearance. The kinetics of glucagon in the fed and fasted group was linear across this large dose range. The mice fed a high-fat diet, however, showed non-linear kinetics with a faster terminal clearance of 20.4±5.45 ml/min (p&lt;0.001) and a shorter elimination half-life of 1.59±0.606 (p&lt;0.001) min relative to normal mice. Conclusions/interpretation: This first systematic dose-ranging study of glucagon kinetics produced several findings: (1) a linear two-compartment model describes glucagon in normal C57BL/6 mice; (2) fasting reduces the clearance of glucagon and (3) high-fat diet enhances the clearance of glucagon. These results may direct future studies on glucagon physiology and indicate that there are other mechanisms, not included in the current model, needed to fully explain glucagon's kinetics.</p>},
  author       = {Zhou, Alyssa and Pacini, Giovanni and Ahrén, Bo and D'Argenio, David Z.},
  issn         = {0012-186X},
  language     = {eng},
  month        = {01},
  number       = {4},
  pages        = {801--808},
  publisher    = {Springer},
  series       = {Diabetologia},
  title        = {Glucagon clearance is regulated by nutritional state : Evidence from experimental studies in mice},
  url          = {http://dx.doi.org/10.1007/s00125-013-3148-x},
  doi          = {10.1007/s00125-013-3148-x},
  volume       = {57},
  year         = {2014},
}