Extraction of Insulin by Liver

Field, J B

doi:10.1146/annurev.me.24.020173.001521

Cited by 139 publications

(67 citation statements)

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“…In the simulated O G T T, the estimated fractional hepatic extraction of insulin is similar to literature values suggesting that ~50% of insulin is extracted by the liver (33). However, in the simulated I V G T T, this value drops to 33% (Ta b l e 1).…”

supporting

confidence: 79%

Accurate measurement of endogenous insulin secretion does not require separate assessment of C-peptide kinetics.

Watanabe

Bergman

2000

Diabetes

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The implication of -cell failure as an early defect in t y p e 2 diabetes exacerbates the need for accurate but facile assessment of islet cell secretory rate, particularly in large group studies in which individual assessment of C-peptide kinetics is impractical. This study was designed to examine whether it is possible to obtain accurate secretory rates from the extended combined model, which provides insulin and C-peptide kinetics from plasma measurements of the two peptides. Equimolar intraportal infusions of insulin and C-peptide that are designed to simulate insulin secretion rates during both oral and intravenous glucose tolerance tests were used to generate plasma insulin and C-peptide data in conscious dogs that were examined under clamped glucose conditions. The plasma peptide kinetics were analyzed using the extended combined model to generate estimates of prehepatic insulin secretion that were then compared with the known intraportal infusion rates. The extended combined model was able to reproduce the known intraportal infusion profiles. The model-predicted rates were similar to those calculated with methods that require separate assessment of C-peptide kinetics. Simulation results supported lesser clearance of insulin during rapid changes of portal insulin (as measured by an intravenous glucose tolerance test) versus slow changes in portal insulin (as measured by an oral glucose tolerance test). The extended combined model accurately calculates prehepatic insulin appearance. It may be possible to apply this approach to large studies of -cell function designed to identify changes in islet function in subjects at risk for diabetes. Such an approach could strengthen epidemiological and genetic studies of the pathogenesis of diabetes. D i a b e t e s 4 9 :3 7 3-382, 2000

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supporting

confidence: 79%

Accurate measurement of endogenous insulin secretion does not require separate assessment of C-peptide kinetics.

Watanabe

Bergman

2000

Diabetes

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“…Nach Stimulation der B-Zelle durch intravenöse Verabreichung von Glucose oder Arginin erreicht das C-Peptid/InsulinVerhältnis in der Portalvene nach 90-120 Sekunden etwa den Wert l, was deutlich macht, daß beide Peptide iii äquimolaren Mengen sezerniert werden (5,6). Die Passage durch die Leber führt -in Abhängigkeit von der Konzentration (7) und offensichtlich als Ausdruck seiner Wirkung (8) -beim Insulin zu einer Extraktion von 50-70% (7,(9)(10)(11)(12)(13)(14), wogegen die hepatische Extraktion von C-Peptid nur gefing ist (l 1). Insulin wird mit einer Halbwertszeit von etwa 5 Minuten (15,16) Studien (13,17) sind neben dem Plasmapool wenigstens zwei weitere Verteilungsräume anzunehmen, ein mit dem Plasma schnell austauschendes Kompartiment, das möglicherweise durch die Organe Leber, Herz und Niere repräsentiert wird, und ein langsam austauschendes Kompartiment, das im wesentlichen den Organen Muskel, Fettgewebe und Haut entsprechen dürfte.…”

Section: Kinetik Und Konzentration Im Plasma Von Proinsulin Insulin unclassified

Pankreatische B-Zellen-Peptide: Kinetik und Konzentration von Proinsulin, Insulin und C-Peptid in Plasma und Urin, Probleme der Meßmethoden, klinische Aussage und Literaturübersicht

Gerbitz¹

1980

CCLM

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Zusammenfassung: Kinetik und Konzentrationen der in Plasma und Urin meßbaren B-Zellen-Peptide werden anhand einer Übersicht der bisher in der Literatur mitgeteilten Daten erläutert und die möglichen Anwendungsgebiete sowie die klinische Aussagekraft der Methoden diskutiert. Allgemeine Probleme der Meßmethoden für freies und antikörper-gebundenes Insulin, Proinsulin und C-Peptid und die möglichen Anwendungsgebiete vor allem im Hinblick auf Diagnostik und Therapie insulinpflichtiger Diabetiker werden dargelegt. Pancreatic B cell peptides: Kinetic behaviour and concentrations ofproinsulin, insulin and C-peptide in plasma and urine, problems of assay methods, clinical significance and literature reviewSummary: The kinetics and the concentrations of B-cell peptides in plasma and urine are reviewed. Methodical problems in the determination of proinsulin, free and antibody-bound insulin and C-peptide are discussed, together with the possible application of these methods in the control of insulin-dependent diabetics. Einführung

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“…In the present study, by direct hepatic vein sampling in healthy humans, we sought to establish the extent of first-pass hepatic insulin extraction and to determine whether the pattern of insulin secretion (insulin pulse mass and amplitude) dictates the hepatic insulin clearance and thereby delivery of insulin to extrahepatic insulin-responsive tissues. Five nondiabetic subjects (two men and three women, mean age 32 years [range 25 F ollowing insulin secretion, the first organ of impact is the liver, where a proportion of secreted insulin is cleared through a receptormediated process (1)(2)(3). The proportion of insulin cleared has been estimated as ϳ50% in dogs (2,4) and ϳ40 -80% in humans (5)(6)(7)(8).…”

mentioning

confidence: 99%

Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

2005

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In health, insulin is secreted in discrete pulses into the portal vein, and the regulation of the rate of insulin secretion is accomplished by modulation of insulin pulse mass. Several lines of evidence suggest that the pattern of insulin delivery by the pancreas determines hepatic insulin clearance. In previous large animal studies, the amplitude of insulin pulses was related to the extent of insulin clearance. In humans (and in large animals), the amplitude of insulin oscillations is ϳ100-fold higher in the portal vein than in the systemic circulation, despite only a fivefold dilution, implying preferential hepatic extraction of insulin pulses. In the present study, by direct hepatic vein sampling in healthy humans, we sought to establish the extent of first-pass hepatic insulin extraction and to determine whether the pattern of insulin secretion (insulin pulse mass and amplitude) dictates the hepatic insulin clearance and thereby delivery of insulin to extrahepatic insulin-responsive tissues.

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Extraction of Insulin by Liver

Cited by 139 publications

References 0 publications

Accurate measurement of endogenous insulin secretion does not require separate assessment of C-peptide kinetics.

Accurate measurement of endogenous insulin secretion does not require separate assessment of C-peptide kinetics.

Pankreatische B-Zellen-Peptide: Kinetik und Konzentration von Proinsulin, Insulin und C-Peptid in Plasma und Urin, Probleme der Meßmethoden, klinische Aussage und Literaturübersicht

Pulsatile Insulin Secretion Dictates Systemic Insulin Delivery by Regulating Hepatic Insulin Extraction In Humans

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