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 W.

AU - Hjort, Line

AU - Gillberg, Linn

AU - Justesen, Louise

AU - Madsbad, Sten

AU - Brøns, Charlotte

AU - Vaag, Allan A.

N1 - Funding Information: The study was funded by the European Foundation for the Study of Diabetes (EFSD), The Danish Council for Strategic Research, Novo Nordisk Fonden, The Danish Diabetes Academy supported by the Novo Nordisk Foundation, The Augustinus Foundation, and The European Union 6th Framework EXGENESIS grant. Publisher Copyright: © 2021 the American Physiological Society.

PY - 2021

Y1 - 2021

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. Thirtysix- 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.

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. Thirtysix- 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.

KW - Fasting

KW - Insulin action

KW - Insulin secretion

KW - Insulin secretion disposition index

KW - Small for gestational age

U2 - 10.1152/AJPENDO.00433.2020

DO - 10.1152/AJPENDO.00433.2020

M3 - Journal article

C2 - 33284087

AN - SCOPUS:85101697279

VL - 320

SP - E281-E290

JO - A J P: Endocrinology and Metabolism (Online)

JF - A J P: Endocrinology and Metabolism (Online)

SN - 1522-1555

IS - 2

ER -