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Impact of prolonged fasting on insulin secretion, insulin action and hepatic versus whole-body insulin secretion disposition indices in healthy young males

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@article{a94964ae78864ba5a3a8ec3a419c9f41,
title = "Impact of prolonged fasting on insulin secretion, insulin action and hepatic versus whole-body insulin secretion disposition indices in healthy young males",
abstract = "The extent to which reduced insulin secretion during prolonged fasting reflects failure to compensate for whole body insulin resistance or a normal adjustment to potentially increased hepatic insulin action is unknown. We examined the effects of 36- versus 12-h fasting on insulin secretion and whole body versus hepatic insulin action in 13 healthy young males. Hepatic glucose production and insulin action were studied using stable isotopes, whereas whole body insulin action and insulin secretion were studied using an intravenous glucose tolerance test (IVGTT) and minimal modeling. Insulin, glucose, and lipid profiles were subsequently measured during a refeeding meal test. Prolonged fasting caused a minor reduction of first-phase insulin secretion in a context of improved hepatic insulin action, contrasting an increase in whole body insulin resistance. Accordingly, prolonged fasting was associated with opposite-directed effects on hepatic versus whole body insulin secretion disposition indices. Thirty-six-hour fasting compared with 12-h fasting was associated with increased serum insulin levels during the refeeding meal test. In conclusion, reduced insulin secretion during prolonged fasting may represent a healthy response to improved hepatic insulin action. Use of insulin secretion disposition indices without taking organ-specific insulin action into account may lead to erroneous conclusions. NEW & NOTEWORTHY Thirty-six-hour prolonged, compared with 12-h overnight fasting, is associated with slightly reduced first-phase insulin secretion in the face of opposite-directed changes in hepatic versus whole body insulin action in healthy young males. The paradoxical finding of increased hepatic versus decreased whole body insulin secretion disposition indices during prolonged fasting challenges the physiological understanding and validity of insulin secretion disposition indices not taking organ-specific insulin action into account. ",
keywords = "Fasting, Insulin action, Insulin secretion, Insulin secretion disposition index, Small for gestational age",
author = "J{\o}rgensen, {Sine Wanda} and Line Hjort and Linn Gillberg and Louise Justesen and Sten Madsbad and Charlotte Br{\o}ns and Allan Vaag",
note = "Publisher Copyright: {\textcopyright} 2021 the American Physiological Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = feb,
day = "1",
doi = "10.1152/AJPENDO.00433.2020",
language = "English",
volume = "320",
pages = "E281--E290",
journal = "American Journal of Physiology: Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "2",

}

RIS

TY - JOUR

T1 - Impact of prolonged fasting on insulin secretion, insulin action and hepatic versus whole-body insulin secretion disposition indices in healthy young males

AU - Jørgensen, Sine Wanda

AU - Hjort, Line

AU - Gillberg, Linn

AU - Justesen, Louise

AU - Madsbad, Sten

AU - Brøns, Charlotte

AU - Vaag, Allan

N1 - Publisher Copyright: © 2021 the American Physiological Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/1

Y1 - 2021/2/1

N2 - The extent to which reduced insulin secretion during prolonged fasting reflects failure to compensate for whole body insulin resistance or a normal adjustment to potentially increased hepatic insulin action is unknown. We examined the effects of 36- versus 12-h fasting on insulin secretion and whole body versus hepatic insulin action in 13 healthy young males. Hepatic glucose production and insulin action were studied using stable isotopes, whereas whole body insulin action and insulin secretion were studied using an intravenous glucose tolerance test (IVGTT) and minimal modeling. Insulin, glucose, and lipid profiles were subsequently measured during a refeeding meal test. Prolonged fasting caused a minor reduction of first-phase insulin secretion in a context of improved hepatic insulin action, contrasting an increase in whole body insulin resistance. Accordingly, prolonged fasting was associated with opposite-directed effects on hepatic versus whole body insulin secretion disposition indices. Thirty-six-hour fasting compared with 12-h fasting was associated with increased serum insulin levels during the refeeding meal test. In conclusion, reduced insulin secretion during prolonged fasting may represent a healthy response to improved hepatic insulin action. Use of insulin secretion disposition indices without taking organ-specific insulin action into account may lead to erroneous conclusions. NEW & NOTEWORTHY Thirty-six-hour prolonged, compared with 12-h overnight fasting, is associated with slightly reduced first-phase insulin secretion in the face of opposite-directed changes in hepatic versus whole body insulin action in healthy young males. The paradoxical finding of increased hepatic versus decreased whole body insulin secretion disposition indices during prolonged fasting challenges the physiological understanding and validity of insulin secretion disposition indices not taking organ-specific insulin action into account.

AB - The extent to which reduced insulin secretion during prolonged fasting reflects failure to compensate for whole body insulin resistance or a normal adjustment to potentially increased hepatic insulin action is unknown. We examined the effects of 36- versus 12-h fasting on insulin secretion and whole body versus hepatic insulin action in 13 healthy young males. Hepatic glucose production and insulin action were studied using stable isotopes, whereas whole body insulin action and insulin secretion were studied using an intravenous glucose tolerance test (IVGTT) and minimal modeling. Insulin, glucose, and lipid profiles were subsequently measured during a refeeding meal test. Prolonged fasting caused a minor reduction of first-phase insulin secretion in a context of improved hepatic insulin action, contrasting an increase in whole body insulin resistance. Accordingly, prolonged fasting was associated with opposite-directed effects on hepatic versus whole body insulin secretion disposition indices. Thirty-six-hour fasting compared with 12-h fasting was associated with increased serum insulin levels during the refeeding meal test. In conclusion, reduced insulin secretion during prolonged fasting may represent a healthy response to improved hepatic insulin action. Use of insulin secretion disposition indices without taking organ-specific insulin action into account may lead to erroneous conclusions. NEW & NOTEWORTHY Thirty-six-hour prolonged, compared with 12-h overnight fasting, is associated with slightly reduced first-phase insulin secretion in the face of opposite-directed changes in hepatic versus whole body insulin action in healthy young males. The paradoxical finding of increased hepatic versus decreased whole body insulin secretion disposition indices during prolonged fasting challenges the physiological understanding and validity of insulin secretion disposition indices not taking organ-specific insulin action into account.

KW - Fasting

KW - Insulin action

KW - Insulin secretion

KW - Insulin secretion disposition index

KW - Small for gestational age

UR - http://www.scopus.com/inward/record.url?scp=85101697279&partnerID=8YFLogxK

U2 - 10.1152/AJPENDO.00433.2020

DO - 10.1152/AJPENDO.00433.2020

M3 - Journal article

C2 - 33284087

VL - 320

SP - E281-E290

JO - American Journal of Physiology: Endocrinology and Metabolism

JF - American Journal of Physiology: Endocrinology and Metabolism

SN - 0193-1849

IS - 2

ER -

ID: 61426860