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Variability of Directly Measured First-Pass Hepatic Insulin Extraction and Its Association With Insulin Sensitivity and Plasma Insulin

Published on Aug 1, 2018in Diabetes7.199
· DOI :10.2337/db17-1520
Isaac Asare-Bediako3
Estimated H-index: 3
(Cedars-Sinai Medical Center),
Rebecca L. Paszkiewicz5
Estimated H-index: 5
(Cedars-Sinai Medical Center)
+ 5 AuthorsRichard N. Bergman96
Estimated H-index: 96
(Cedars-Sinai Medical Center)
Abstract
Although the β-cells secrete insulin, the liver, with its first-pass insulin extraction (FPE), regulates the amount of insulin allowed into circulation for action on target tissues. The metabolic clearance rate of insulin, of which FPE is the dominant component, is a major determinant of insulin sensitivity (SI). We studied the intricate relationship among FPE, SI, and fasting insulin. We used a direct method of measuring FPE, the paired portal/peripheral infusion protocol, where insulin is infused stepwise through either the portal vein or a peripheral vein in healthy young dogs ( n = 12). FPE is calculated as the difference in clearance rates (slope of infusion rate vs. steady insulin plot) between the paired experiments. Significant correlations were found between FPE and clamp-assessed SI ( r s = 0.74), FPE and fasting insulin ( r s = −0.64), and SI and fasting insulin ( r s = −0.67). We also found a wide variance in FPE (22.4–77.2%; mean ± SD 50.4 ± 19.1) that is reflected in the variability of plasma insulin (48.1 ± 30.9 pmol/L) and SI (9.4 ± 5.8 × 10 4 dL · kg −1 · min −1 · [pmol/L] −1 ). FPE could be the nexus of regulation of both plasma insulin and SI.
  • References (50)
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African Americans (AAs) tend to have higher plasma insulin concentrations than European Americans (EAs); the increased insulin concentrations have been attributed to increased secretion and/or decreased insulin clearance by liver or other tissues. This work characterizes the contributions of hepatic versus extrahepatic insulin degradation related to ethnic differences between AAs and EAs. By using a recently developed mathematical model that uses insulin and C-peptide measurements from the insul...
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