Hepatic and Extrahepatic Insulin Clearance in Mice with Double Deletion of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Receptors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Assessment of Hepatic and Extrahepatic Insulin Clearance
2.3. Assessment of Other Parameters of Glucose Metabolism
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
AIRG | Acute Insulin Response to glucose |
AUCCP | Area Under the Curve of C-peptide |
AUCI | Area Under the Curve of insulin |
AUCSECR | Area Under the Curve of insulin secretion rate |
CEACAM1 | Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 |
CLCP | C-peptide clearance during IVGTT |
CLP-P1 | Extrahepatic insulin clearance in the first phase of IVGTT |
CLP-P2 | Extrahepatic insulin clearance in the second phase of IVGTT |
CLT-P1 | Total insulin clearance in the first phase of IVGTT |
CLT-P2 | Total insulin clearance in the second phase of IVGTT |
DI | Disposition Index |
DIRKO | Double Incretin Receptor KnockOut |
EICR(t) | Extrahepatic Insulin Clearance Rate |
FEL-P1 | Hepatic insulin clearance in the first phase of IVGTT |
FEL-P2 | Hepatic insulin clearance in the second phase of IVGTT |
GIP | Glucose-dependent insulinotropic polypeptide |
GLP-1 | Glucagon-like Peptide 1 |
HICR(t) | Hepatic Insulin Clearance Rate |
HPF | Hepatic Plasma Flow |
I(t) | Plasma insulin concentration |
IDE | Insulin-Degrading Enzyme |
ISR(t) | Insulin Secretion Rate |
IVGTT | Intravenous Glucose Tolerance Test |
KG | Glucose tolerance |
QUICKI | Quantitative Insulin Sensitivity Check Index |
SI | Insulin sensitivity during the IVGTT |
SG | Glucose effectiveness |
SNX | Sorting Nexin |
tfin | Final time of IVGTT |
tini | Initial time of IVGTT |
V | Distribution volume |
WT | Wild-Type |
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WT | DIRKO | p-Value | ||
---|---|---|---|---|
First phase | FEL-P1 (%) | 28.9 [25.7–32.0] | 29.7 [26.7–34.9] | 0.18 |
CLP-P1 (10−3 l∙min−1) | 0.15 [0.11–0.22] | 0.18 [0.13–0.27] * | 0.04 | |
CLT-P1 (10−3 l∙min−1) | 0.51 [0.46–0.65] | 0.61 [0.48–0.82] * | 0.02 | |
Second phase | FEL-P2 (%) | 39.8 [35.8–44.2] | 37.8 [35.1–43.1] | 0.46 |
CLP-P2 (10−3 l∙min−1) | 0.79 [0.69–0.87] | 0.72 [0.64–0.81] | 0.27 | |
CLT-P2 (10−3 l∙min−1) | 1.69 [1.48–1.87] | 1.38 [1.13–1.75] | 0.10 |
WT | DIRKO | p-Value | |
---|---|---|---|
KG (%/min) | 2.49 [1.85–3.14] | 1.98 [0.96–2.41] * | <0.01 |
SI (10−4 min−1/pmol/l) | 1.37 [0.97–1.78] | 0.85 [0.77–1.39] * | <0.01 |
QUICKI (dimensionless) | 0.123 [0.119–0.126] | 0.120 [0.116–0.123] | 0.07 |
SG (min−1) | 0.052 [0.037–0.063] | 0.037 [0.028–0.055] * | 0.02 |
AIRG (pmol/l) | 445 [288–635] | 426 [195–634] | 0.16 |
DI (10−3 min−1) | 1.17 [0.70–1.64] | 0.72 [0.34–1.03] * | 0.02 |
AUCSECR (pmol) | 13.0 [12.0–16.8] | 17.0 [14.3–21.0] * | <0.01 |
β-cell sensitivity (mmol C-peptide/mmol Glucose) | 0.022 [0.018–0.027] | 0.025 [0.021–0.030] | 0.05 |
First Phase | Second Phase | ||||||
---|---|---|---|---|---|---|---|
FEL-P1 | CLP-P1 | CLT-P1 | FEL-P2 | CLP-P2 | CLT-P2 | ||
WT + DIRKO | KG | n.s. | 0.08 (0.01) | 0.08 (0.01) | 0.08 (0.01) | n.s. | 0.07 (0.03) |
SI | n.s. | n.s. | n.s. | n.s. | n.s. | n.s. | |
QUICKI | 0.06 (0.02) | 0.10 (<0.01) | 0.12 (<0.01) | n.s. | n.s. | n.s. | |
SG | n.s. | n.s. | n.s. | 0.06 (0.03) | n.s. | n.s. | |
AIRG | 0.37 (<0.001) | 0.59 (<0.001) | 0.60 (<0.001) | n.s. | n.s. | n.s. | |
DI | 0.23 (<0.001) | 0.38 (<0.001) | 0.39 (<0.01) | 0.07 (0.02) | n.s. | n.s. | |
AUCSECR | 0.07 (0.02) | 0.13 (<0.01) | 0.12 (<0.01) | 0.17 (<0.001) | n.s. | n.s. | |
β-cell sensitivity | 0.06 (0.03) | 0.11 (<0.01) | 0.11 (<0.01) | n.s. | n.s. | 0.11 (<0.01) | |
WT | KG | n.s. | n.s. | n.s. | n.s. | n.s. | n.s. |
SI | n.s. | n.s. | n.s. | n.s. | n.s. | n.s. | |
QUICKI | n.s. | n.s. | n.s. | n.s. | n.s. | n.s. | |
SG | n.s. | n.s. | n.s. | n.s. | n.s. | n.s. | |
AIRG | 0.51 (<0.001) | 0.62 (<0.001) | 0.62 (<0.001) | n.s. | n.s. | n.s. | |
DI | 0.33 (<0.001) | 0.40 (<0.001) | 0.40 (<0.001) | n.s. | n.s. | n.s. | |
AUCSECR | 0.15 (<0.01) | 0.14 (0.01) | 0.15 (<0.01) | 0.15 (<0.01) | n.s. | n.s. | |
β-cell sensitivity | 0.16 (<0.01) | 0.22 (<0.01) | 0.23 (<0.001) | n.s. | n.s. | 0.11 (0.03) | |
DIRKO | KG | n.s. | n.s. | n.s. | n.s. | n.s. | 0.14 (0.04) |
SI | n.s. | n.s. | n.s. | n.s. | n.s. | n.s. | |
QUICKI | n.s. | n.s. | n.s. | n.s. | n.s. | n.s. | |
SG | n.s. | n.s. | n.s. | n.s. | n.s. | n.s. | |
AIRG | 0.19 (0.01) | 0.56 (<0.001) | 0.60 (<0.001) | n.s. | n.s. | 0.19 (0.01) | |
DI | n.s. | 0.29 (<0.01) | 0.31 (<0.01) | n.s. | n.s. | 0.26 (<0.01) | |
AUCSECR | n.s. | n.s. | n.s. | 0.37 (<0.001) | n.s. | 0.15 (0.03) | |
β-cell sensitivity | n.s. | n.s. | n.s. | n.s. | n.s. | n.s. |
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Morettini, M.; Piersanti, A.; Burattini, L.; Pacini, G.; Göbl, C.; Ahrén, B.; Tura, A. Hepatic and Extrahepatic Insulin Clearance in Mice with Double Deletion of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Receptors. Biomedicines 2021, 9, 973. https://doi.org/10.3390/biomedicines9080973
Morettini M, Piersanti A, Burattini L, Pacini G, Göbl C, Ahrén B, Tura A. Hepatic and Extrahepatic Insulin Clearance in Mice with Double Deletion of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Receptors. Biomedicines. 2021; 9(8):973. https://doi.org/10.3390/biomedicines9080973
Chicago/Turabian StyleMorettini, Micaela, Agnese Piersanti, Laura Burattini, Giovanni Pacini, Christian Göbl, Bo Ahrén, and Andrea Tura. 2021. "Hepatic and Extrahepatic Insulin Clearance in Mice with Double Deletion of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Receptors" Biomedicines 9, no. 8: 973. https://doi.org/10.3390/biomedicines9080973