Hepatic and extrahepatic insulin clearance in mice with double deletion of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors
(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)
- author
- Morettini, Micaela ; Piersanti, Agnese ; Burattini, Laura ; Pacini, Giovanni ; Göbl, Christian ; Ahrén, Bo LU and Tura, Andrea
- organization
- publishing date
- 2021-08
- 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
-
- pmid:34440177
- scopus:85112437827
- 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
- 2024-10-06 04:34:15
@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}}, }