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Postprandial aminogenic insulin and glucagon secretion can stimulate glucose flux in humans
journal contribution
posted on 2019-05-01, 00:00 authored by Teddy Ang, Clinton BruceClinton Bruce, Greg KowalskiGreg KowalskiInsulin and glucagon exert opposing actions on glucose metabolism and their secretion is classically viewed as being inversely regulated. This is, however, context specific as protein ingestion concomitantly stimulates euglycemic insulin and glucagon secretion. It remains enigmatic how euglycemia is preserved under these conditions. Accordingly, we examined the systems-level mechanisms governing such endocrine control of glucose homeostasis. Eight healthy participants completed a water (control) and multi-dose whey protein ingestion trial designed to augment the protein-induced endocrine response. Glucose kinetics were measured using stable isotope tracer methodology. Protein ingestion induced marked hyperaminoacidemia, hyperinsulinemia (∼6-fold basal) and unprecedented hyperglucagonemia (∼8-fold basal) whilst suppressing free fatty acids. Both glucose disposal (Rd) and endogenous glucose production (EGP) increased by ∼25%, thereby maintaining euglycemia. This demonstrates: 1) protein ingestion can stimulate glucose Rd and EGP; 2) postprandial inhibition of adipose lipolysis does not suppress EGP; and 3) physiological hyperglucagonemia can override the hepatic actions of insulin, rendering the liver unresponsive to insulin-mediated EGP suppression. Finally, we argue that glucagon is a bona fide postprandial hormone that evolved to concurrently and synergistically work with insulin to regulate glucose, amino acid and nitrogen metabolism. These findings may have implications for glucagon receptor antagonist or agonist-based therapies.
History
Journal
DiabetesVolume
68Issue
5Pagination
939 - 946Publisher
American Diabetes AssociationLocation
Arlington, Va.Publisher DOI
eISSN
1939-327XLanguage
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2019, The American Diabetes AssociationUsage metrics
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