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

Diabetes
Isaac Asare-BediakoRichard N Bergman

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 (rs = 0.74), FPE and fasting insulin (rs = -0.64), and SI and fasting insulin (rs = -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 × 104 dL · kg-1 · min-1 · [pmol/L]-1). FPE could be the nexus of regulation of both plasma insulin and SI.

References

Feb 1, 1988·The Journal of Clinical Investigation·K S PolonskyE Van Cauter
Apr 1, 1987·Diabetes/metabolism Reviews·E Ferrannini, C Cobelli
Jan 1, 1985·Endocrine Reviews·R N BergmanM Ader
Aug 1, 1966·The American Journal of Physiology·Y KanazawaK Kosaka
Feb 1, 1984·Metabolism: Clinical and Experimental·P R Bratusch-MarrainA Hofer
Aug 1, 1984·The Journal of Clinical Endocrinology and Metabolism·L SaccàC Vigorito
May 1, 1983·Metabolism: Clinical and Experimental·E BonoraU Butturini
Sep 1, 1983·The Journal of Clinical Investigation·K PolonskyA H Rubenstein
Aug 1, 1996·The Journal of Clinical Investigation·K RebrinR N Bergman
Mar 31, 1999·Human Reproduction Update·M CiampelliA Caruso
Jan 5, 2001·BMJ : British Medical Journal·I J Beckingham, S D Ryder
Feb 19, 2002·Nature Genetics·Matthew N PoySonia M Najjar
Nov 12, 2002·Nature Medicine·Silvana ObiciLuciano Rossetti
Jun 28, 1954·The Journal of Physiology·E P HELPS, D A McDONALD
Jul 1, 1956·Circulation Research·L A SAPIRSTEIN, E J REININGER
Dec 14, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lixia ZhaoGreg M Cole
Dec 14, 2005·Postgraduate Medical Journal·M C Marshall
Feb 8, 2007·American Journal of Physiology. Endocrinology and Metabolism·Stella P KimRichard N Bergman
Jan 4, 2008·American Journal of Physiology. Endocrinology and Metabolism·Johannes ErdmannVolker Schusdziarra
Jan 27, 2009·Obesity·Clifton Bogardus
Oct 8, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Natalia RudovichAndreas F H Pfeiffer
Jul 29, 2017·Journal of Diabetes Investigation·Hirotaka Watada, Yoshifumi Tamura

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Citations

Apr 11, 2019·Physiology·Sonia M Najjar, Germán Perdomo
Jun 4, 2020·Diabetes, Obesity & Metabolism·Meera LadwaLouise M Goff
Jan 28, 2019·International Journal of Adolescent Medicine and Health·Aminolah VasighAsma Tarjoman
Jun 27, 2019·Endocrine Reviews·Jonathan D DourosDavid A D'Alessio
Sep 11, 2020·Diabetes Care·Francesca Piccinini, Richard N Bergman
Feb 7, 2020·Medicine and Science in Sports and Exercise·Adithya HariJohn P Kirwan
Mar 5, 2021·Frontiers in Endocrinology·Richard N Bergman
May 11, 2021·Frontiers in Endocrinology·Erwin Ilegems, Per-Olof Berggren

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Methods Mentioned

BETA
biopsy
ELISA
PCR

Software Mentioned

PPII

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