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The liver and glycogen metabolism.
1Diabetes and Metabolism Research Laboratory, University of Ottawa, Ontario, Canada.
Summary
The liver doesn't primarily clear glucose post-meal. Instead, lactate from sources like the gut is crucial for forming liver glycogen, highlighting a key metabolic pathway.
Area of Science:
- Biochemistry
- Human Physiology
- Animal Models
Background:
- The liver's role in glucose metabolism after carbohydrate intake is significant.
- Previous understanding suggested the liver was the primary site for glucose removal post-meal.
- The exact substrates for hepatic glycogen synthesis require further investigation.
Purpose of the Study:
- To identify the primary substrates for hepatic glycogen synthesis after a carbohydrate meal.
- To investigate the contribution of lactate to postprandial liver glycogen formation.
- To elucidate the metabolic pathways involved in glucose homeostasis.
Main Methods:
- Utilized differential blood sampling across the liver and gut in a conscious pig model.
- Measured fractional extraction of substrates, specifically lactate.
- Analyzed lactate contribution from various tissues, including the gut and forearm muscle.
Main Results:
- The liver's fractional extraction of glucose post-meal is low (5-10%).
- Approximately 60% of hepatic glycogen is synthesized from gluconeogenetic substrates.
- The liver extracts significant amounts of lactate (40-50% fractional extraction), with 40% originating from the gut.
- Forearm muscle does not contribute lactate during glucose loading.
Conclusions:
- Lactate, particularly from the gut, is a major gluconeogenetic substrate for hepatic glycogen synthesis post-meal.
- Non-hepatic tissues, potentially skin, contribute to lactate production during glucose loading.
- Gluconeogenesis may represent a significant pathway for obligatory lactate production in tissues.