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The effect of ingested glucose dose on the suppression of endogenous glucose production in humans
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posted on 2017-01-01, 00:00 authored by Greg KowalskiGreg Kowalski, Samantha MooreSamantha Moore, Steven Hamley, Ahrathy SelathuraiAhrathy Selathurai, Clinton BruceClinton BruceInsulin clamp studies have shown that the suppressive actions of insulin on endogenous glucose production (EGP) are markedly more sensitive than for stimulating glucose disposal (Rd). However, clamp conditions do not adequately mimic postprandial physiological responses. Here, using the variable infusion dual-tracer approach, we used a threefold range of ingested glucose doses (25, 50, and 75 g) to investigate how physiological changes in plasma insulin influence EGP in healthy subjects. Remarkably, the glucose responses were similar for all doses tested, yet there was a dose-dependent increase in insulin secretion and plasma insulin levels. Nonetheless, EGP was suppressed with the same rapidity and magnitude (∼55%) across all doses. The progressive hyperinsulinemia, however, caused a dose-dependent increase in the estimated rates of Rd, which likely accounts for the lack of a dose effect on plasma glucose excursions. This suggests that after glucose ingestion, the body preferentially permits a transient and optimal degree of postprandial hyperglycemia to efficiently enhance insulin-induced changes in glucose fluxes, thereby minimizing the demand for insulin secretion. This may represent an evolutionarily conserved mechanism that not only reduces the secretory burden on β-cells but also avoids the potential negative consequences of excessive insulin release into the systemic arterial circulation.
History
Journal
DiabetesVolume
66Issue
9Pagination
2400 - 2406Publisher
American Diabetes AssociationLocation
Arlington County, Va.Publisher DOI
eISSN
1939-327XLanguage
engPublication classification
C Journal article; C1 Refereed article in a scholarly journalCopyright notice
2017, The American Diabetes AssociationUsage metrics
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