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
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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
L-P1, CL
P-P1; FE
L-P2, CL
P-P2) accounting for hepatic and extrahepatic clearance in the IVGTT first and second phases, respectively, plus the respective total clearances, CL
T-P1 and CL
T-P2. A statistically significant difference between DIRKO and WT was found in CL
T-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, CL
P-P1 (0.18 [0.13–0.27] vs. 0.15 [0.11–0.22];
p = 0.04), but not in the hepatic component, FE
L-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 CL
T-P2 (1.38 [1.13–1.75] vs. 1.69 [1.48–1.87];
p = 0.10), neither in CL
P-P2 (0.72 [0.64–0.81] vs. 0.79 [0.69–0.87];
p = 0.27) nor in FE
L-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.
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