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Increased insulin clearance in mice with double deletion of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors

Tura, Andrea ; Bizzotto, Roberto ; Yamada, Yuchiro ; Seino, Yutaka ; Pacini, Giovanni and Ahrén, Bo LU (2018) In American Journal of Physiology - Regulatory Integrative and Comparative Physiology 314(5). p.639-646
Abstract

To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO (n = 31) and wild-type (WT) C57BL6J mice (n = 45) were intravenously injected with D-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for glucose, insulin, and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection. Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 ± 0.10 10–31/min. After... (More)

To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO (n = 31) and wild-type (WT) C57BL6J mice (n = 45) were intravenously injected with D-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for glucose, insulin, and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection. Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 ± 0.10 10–31/min. After intravenous glucose administration, insulin clearance during first phase insulin secretion was markedly higher in DIRKO than in WT mice (0.68 ± 0.06 10–3l/min in DIRKO mice vs. 0.54 ± 0.03 10–31/min in WT mice, P = 0.02). In contrast, there was no difference between the two groups in insulin clearance during second phase insulin secretion (P = 0.18). In conclusion, this study evaluated C-peptide kinetics in the mouse and exploited a mathematical model to estimate insulin clearance. Results showed that DIRKO mice have higher insulin clearance than WT mice, following intravenous injection of glucose. This suggests that incretin hormones reduce insulin clearance at physiological, nonstimulated levels.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animal model, Incretin hormones, Insulin clearance, Insulin secretion, Mathematical model
in
American Journal of Physiology - Regulatory Integrative and Comparative Physiology
volume
314
issue
5
pages
639 - 646
publisher
American Physiological Society
external identifiers
  • scopus:85046898337
  • pmid:29351421
ISSN
0363-6119
DOI
10.1152/ajpregu.00181.2017
language
English
LU publication?
yes
id
0f8e7cb3-246d-4ea9-9eff-0ef608f2e209
date added to LUP
2018-05-24 14:16:54
date last changed
2021-06-08 02:39:12
@article{0f8e7cb3-246d-4ea9-9eff-0ef608f2e209,
  abstract     = {<p>To establish whether incretin hormones affect insulin clearance, the aim of this study was to assess insulin clearance in mice with genetic deletion of receptors for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO). DIRKO (n = 31) and wild-type (WT) C57BL6J mice (n = 45) were intravenously injected with D-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for glucose, insulin, and C-peptide. Data were modeled to calculate insulin clearance; C-peptide kinetics was established after human C-peptide injection. Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 ± 0.10 10<sup>–3</sup>1/min. After intravenous glucose administration, insulin clearance during first phase insulin secretion was markedly higher in DIRKO than in WT mice (0.68 ± 0.06 10<sup>–3</sup>l/min in DIRKO mice vs. 0.54 ± 0.03 10<sup>–3</sup>1/min in WT mice, P = 0.02). In contrast, there was no difference between the two groups in insulin clearance during second phase insulin secretion (P = 0.18). In conclusion, this study evaluated C-peptide kinetics in the mouse and exploited a mathematical model to estimate insulin clearance. Results showed that DIRKO mice have higher insulin clearance than WT mice, following intravenous injection of glucose. This suggests that incretin hormones reduce insulin clearance at physiological, nonstimulated levels.</p>},
  author       = {Tura, Andrea and Bizzotto, Roberto and Yamada, Yuchiro and Seino, Yutaka and Pacini, Giovanni and Ahrén, Bo},
  issn         = {0363-6119},
  language     = {eng},
  month        = {05},
  number       = {5},
  pages        = {639--646},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology - Regulatory Integrative and Comparative Physiology},
  title        = {Increased insulin clearance in mice with double deletion of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors},
  url          = {http://dx.doi.org/10.1152/ajpregu.00181.2017},
  doi          = {10.1152/ajpregu.00181.2017},
  volume       = {314},
  year         = {2018},
}