Decreased basal hepatic glucose uptake in impaired fasting glucose
This research aimed to define the pathophysiological defects responsible for the elevated fasting plasma glucose (FPG) concentration and excessive rise in post-load plasma glucose observed in individuals with impaired fasting glucose (IFG).
We used tracer techniques to quantify basal splanchnic (primarily hepatic) glucose uptake and glucose fluxes following glucose ingestion in individuals with normal glucose tolerance (NGT; n = 10) and IFG (n = 10).
Individuals with IFG had a comparable basal rate of hepatic glucose production to those with NGT (15.2 ± 0.2 vs 18.0 ± 0.8 μmol min−1 [kg lean body mass (LBM)]−1; p = 0.09). However, they had a significantly reduced glucose clearance rate during the fasting state compared with NGT (2.64 ± 0.11 vs 3.62 ± 0.20 ml min−1 [kg LBM]−1; p < 0.01). The difference between the basal rate of glucose appearance measured with [3-3H]glucose and [1-14C]glucose, which represent basal splanchnic glucose uptake, was significantly reduced in IFG compared with NGT (1.39 ± 0.28 vs 3.16 ± 0.44 μmol min−1 [kg LBM]−1; p = 0.02). Following glucose ingestion, the total amount of exogenous glucose that appeared in the systemic circulation was not significantly different between groups. However, suppression of endogenous glucose production (EGP) was markedly impaired in individuals with IFG.
These results demonstrate that decreased tissue (liver) glucose uptake, not enhanced EGP, is the cause for elevated FPG concentration in individuals with IFG, while the excessive rise in plasma glucose concentration following a glucose load in these individuals is the result of impaired suppression of hepatic glucose production.
KeywordsHepatic glucose production Hepatic glucose uptake Impaired fasting glucose
Basal rate of endogenous glucose production
Endogenous glucose production
Fasting plasma glucose
Hepatic glucose uptake
Impaired fasting glucose
Impaired glucose tolerance
Lean body mass
Normal glucose tolerance
Rate of appearance
Residual rate of endogenous glucose production
Rate of appearance of oral glucose
Total rate of appearance of glucose in the systemic circulation
|Funder Name||Grant Number||Funding Note|
|NIH grant (R01 DK097554-01) to MAG|