Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Morettini, Micaela ; Piersanti, Agnese ; Burattini, Laura ; Pacini, Giovanni ; Göbl, Christian ; Ahrén, Bo LU and Tura, Andrea (2021) In Biomedicines 9(8).
Abstract

The aim of this study was to investigate whether incretins, at physiological levels, affect hepatic and/or extrahepatic insulin clearance. Hepatic and extrahepatic insulin clearance was studied in 31 double incretin receptor knockout (DIRKO) and 45 wild-type (WT) mice, which underwent an Intravenous Glucose Tolerance Test (IVGTT). A novel methodology based on mathematical modeling was designed to provide two sets of values (FEL-P1, CLP-P1; FEL-P2, CLP-P2 ) accounting for hepatic and extrahepatic clearance in the IVGTT first and second phases, respectively, plus the respective total clearances, CLT-P1 and CLT-P2 . A statistically significant difference between DIRKO and WT... (More)

The aim of this study was to investigate whether incretins, at physiological levels, affect hepatic and/or extrahepatic insulin clearance. Hepatic and extrahepatic insulin clearance was studied in 31 double incretin receptor knockout (DIRKO) and 45 wild-type (WT) mice, which underwent an Intravenous Glucose Tolerance Test (IVGTT). A novel methodology based on mathematical modeling was designed to provide two sets of values (FEL-P1, CLP-P1; FEL-P2, CLP-P2 ) accounting for hepatic and extrahepatic clearance in the IVGTT first and second phases, respectively, plus the respective total clearances, CLT-P1 and CLT-P2 . A statistically significant difference between DIRKO and WT was found in CLT-P1 (0.61 [0.48–0.82] vs. 0.51 [0.46–0.65] (median [interquartile range]); p = 0.02), which was reflected in the peripheral component, CLP-P1 (0.18 [0.13–0.27] vs. 0.15 [0.11–0.22]; p = 0.04), but not in the hepatic component, FEL-P1 (29.7 [26.7–34.9] vs. 28.9 [25.7–32.0]; p = 0.18). No difference was detected between DIRKO and WT in CLT-P2 (1.38 [1.13–1.75] vs. 1.69 [1.48–1.87]; p = 0.10), neither in CLP-P2 (0.72 [0.64–0.81] vs. 0.79 [0.69–0.87]; p = 0.27) nor in FEL-P2 (37.8 [35.1–43.1] vs. 39.8 [35.8–44.2]; p = 0.46). In conclusion, our findings suggest that the higher insulin clearance observed in DIRKO compared with WT during the IVGTT first phase may be due to its extrahepatic component.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animal model, DIRKO, Incretin hormones, Insulin clearance, IVGTT, Mathematical model
in
Biomedicines
volume
9
issue
8
article number
973
publisher
MDPI AG
external identifiers
  • scopus:85112437827
  • pmid:34440177
ISSN
2227-9059
DOI
10.3390/biomedicines9080973
language
English
LU publication?
yes
id
5364c862-893f-44fd-a602-8c8559379f96
date added to LUP
2021-09-23 11:29:57
date last changed
2024-06-15 16:41:22
@article{5364c862-893f-44fd-a602-8c8559379f96,
  abstract     = {{<p>The aim of this study was to investigate whether incretins, at physiological levels, affect hepatic and/or extrahepatic insulin clearance. Hepatic and extrahepatic insulin clearance was studied in 31 double incretin receptor knockout (DIRKO) and 45 wild-type (WT) mice, which underwent an Intravenous Glucose Tolerance Test (IVGTT). A novel methodology based on mathematical modeling was designed to provide two sets of values (FE<sub>L-P1</sub>, CL<sub>P-P1</sub>; FE<sub>L-P2</sub>, CL<sub>P-P2</sub> ) accounting for hepatic and extrahepatic clearance in the IVGTT first and second phases, respectively, plus the respective total clearances, CL<sub>T-P1</sub> and CL<sub>T-P2</sub> . A statistically significant difference between DIRKO and WT was found in CL<sub>T-P1</sub> (0.61 [0.48–0.82] vs. 0.51 [0.46–0.65] (median [interquartile range]); p = 0.02), which was reflected in the peripheral component, CL<sub>P-P1</sub> (0.18 [0.13–0.27] vs. 0.15 [0.11–0.22]; p = 0.04), but not in the hepatic component, FE<sub>L-P1</sub> (29.7 [26.7–34.9] vs. 28.9 [25.7–32.0]; p = 0.18). No difference was detected between DIRKO and WT in CL<sub>T-P2</sub> (1.38 [1.13–1.75] vs. 1.69 [1.48–1.87]; p = 0.10), neither in CL<sub>P-P2</sub> (0.72 [0.64–0.81] vs. 0.79 [0.69–0.87]; p = 0.27) nor in FE<sub>L-P2</sub> (37.8 [35.1–43.1] vs. 39.8 [35.8–44.2]; p = 0.46). In conclusion, our findings suggest that the higher insulin clearance observed in DIRKO compared with WT during the IVGTT first phase may be due to its extrahepatic component.</p>}},
  author       = {{Morettini, Micaela and Piersanti, Agnese and Burattini, Laura and Pacini, Giovanni and Göbl, Christian and Ahrén, Bo and Tura, Andrea}},
  issn         = {{2227-9059}},
  keywords     = {{Animal model; DIRKO; Incretin hormones; Insulin clearance; IVGTT; Mathematical model}},
  language     = {{eng}},
  number       = {{8}},
  publisher    = {{MDPI AG}},
  series       = {{Biomedicines}},
  title        = {{Hepatic and extrahepatic insulin clearance in mice with double deletion of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors}},
  url          = {{http://dx.doi.org/10.3390/biomedicines9080973}},
  doi          = {{10.3390/biomedicines9080973}},
  volume       = {{9}},
  year         = {{2021}},
}