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

Overview

Journal Diabetes

Specialty Endocrinology

Date 2018 May 13

PMID 29752425

Citations 22

Authors

Isaac Asare-Bediako

Rebecca L Paszkiewicz

Stella P Kim

Orison O Woolcott

Cathryn M Kolka

Miguel A Burch

Morvarid Kabir

Richard N Bergman

Affiliations

Soon will be listed here.

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 ( = 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 ( = 0.74), FPE and fasting insulin ( = -0.64), and SI and fasting insulin ( = -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 dL · kg · min · [pmol/L]). FPE could be the nexus of regulation of both plasma insulin and SI.

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