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Postprandial aminogenic insulin and glucagon secretion can stimulate glucose flux in humans

Version 2 2024-06-04, 03:33
Version 1 2019-03-07, 07:54
journal contribution
posted on 2024-06-04, 03:33 authored by T Ang, Clinton BruceClinton Bruce, Greg KowalskiGreg Kowalski
Insulin 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 multidose 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 (approximately sixfold basal), and unprecedented hyperglucagonemia (approximately eightfold basal) while suppressing free fatty acids. Both glucose disposal (Rd) and endogenous glucose production (EGP) increased by ∼25%, thereby maintaining euglycemia. This demonstrates 1) that protein ingestion can stimulate glucose Rd and EGP, 2) that postprandial inhibition of adipose lipolysis does not suppress EGP, and 3) that 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

Diabetes

Volume

68

Pagination

939-946

Location

United States

ISSN

0012-1797

eISSN

1939-327X

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2019, The American Diabetes Association

Issue

5

Publisher

AMER DIABETES ASSOC

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