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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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.
Original language | English |
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Journal | American Journal of Physiology - Endocrinology and Metabolism |
Volume | 320 |
Issue number | 2 |
Pages (from-to) | E281-E290 |
Number of pages | 10 |
ISSN | 0193-1849 |
DOIs | |
Publication status | Published - 2021 |
Bibliographical note
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.
- Fasting, Insulin action, Insulin secretion, Insulin secretion disposition index, Small for gestational age
Research areas
ID: 281107146